id
stringlengths 11
17
| article_id
stringlengths 8
11
| path
stringlengths 11
60
| section_title
stringlengths 1
1.33k
| educational_score
float64 0
5.16
| domain
stringclasses 4
values | document_type
stringclasses 5
values | domain_scores
listlengths 0
3
| document_type_scores
listlengths 0
4
| text
stringlengths 1
110k
| authors
listlengths 0
8.02k
| article_url
stringlengths 3
63
| license_type
stringclasses 1
value | license_url
stringclasses 15
values | language
stringclasses 45
values | language_score
float64 0
1
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PMC11277181_p2
|
PMC11277181
|
sec[1]/p[0]
|
Case presentation
| 3.740234 |
clinical
|
Clinical case
|
[
0.1295166015625,
0.86572265625,
0.00492095947265625
] |
[
0.004192352294921875,
0.0096893310546875,
0.00323486328125,
0.98291015625
] |
A newborn male with a strong genetic predisposition to WS was born prematurely at 35 weeks of gestation via urgent cesarean section due to complications, including meconium aspiration, gestational hypertension, and maternal diabetes mellitus. He weighed 3400 grams at birth. The delivery required immediate resuscitative measures as the infant was flaccid and cyanosed. Apgar scores were 2 and 6 at one and five minutes, respectively, and special management of an umbilical cord injury was necessary.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277181_p3
|
PMC11277181
|
sec[1]/p[1]
|
Case presentation
| 3.652344 |
clinical
|
Clinical case
|
[
0.08636474609375,
0.91015625,
0.0033016204833984375
] |
[
0.00566864013671875,
0.012237548828125,
0.00261688232421875,
0.9794921875
] |
Upon admission to the neonatal intensive care unit (NICU), the infant exhibited symptoms consistent with transient tachypnea of the newborn (TTN). The initial assessment revealed moderate respiratory distress characterized by mild subcostal and intercostal retractions, with an initial oxygen saturation of 88% on room air. Echocardiography showed no evidence of persistent pulmonary hypertension of the newborn (PPHN). Given the clinical picture, the infant was promptly admitted to the NICU for specialized care.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p4
|
PMC11277181
|
sec[1]/p[2]
|
Case presentation
| 3.869141 |
clinical
|
Clinical case
|
[
0.275634765625,
0.72265625,
0.0017576217651367188
] |
[
0.08709716796875,
0.269287109375,
0.007335662841796875,
0.63623046875
] |
Treatment began with supplemental oxygen via nasal cannula, but due to worsening respiratory status, including increased work of breathing and intermittent desaturation, it was intensified to endotracheal intubation and mechanical ventilation. The highest ventilator settings recorded were a peak inspiratory pressure (PIP) of 20 cm H2O, positive end-expiratory pressure (PEEP) of 4 cm H2O, a fraction of inspired oxygen (FiO2) of 40%, and a rate of 30 breaths per minute.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p5
|
PMC11277181
|
sec[1]/p[3]
|
Case presentation
| 2.25 |
clinical
|
Clinical case
|
[
0.1629638671875,
0.83154296875,
0.00548553466796875
] |
[
0.0033397674560546875,
0.0205535888671875,
0.0016536712646484375,
0.974609375
] |
Initial radiographs showed diffuse pulmonary haziness and a slightly enlarged heart, consistent with TTN, but these abnormalities gradually resolved with continued supportive care .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p6
|
PMC11277181
|
sec[1]/p[4]
|
Case presentation
| 3.474609 |
clinical
|
Clinical case
|
[
0.1551513671875,
0.84228515625,
0.002498626708984375
] |
[
0.016204833984375,
0.038360595703125,
0.0028076171875,
0.9423828125
] |
Despite standard ventilatory support, the infant continued to struggle with hypoxemia. This led to a brief period of high-frequency oscillatory (HFO) ventilation before a return to conventional methods. Alongside surfactant therapy, the medical team made frequent adjustments to the ventilatory settings, closely monitored blood gas levels (Table 1 ), and conducted serial chest X-rays .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277181_p7
|
PMC11277181
|
sec[1]/p[5]
|
Case presentation
| 3.824219 |
clinical
|
Clinical case
|
[
0.12066650390625,
0.87744140625,
0.00200653076171875
] |
[
0.0142364501953125,
0.021392822265625,
0.0032787322998046875,
0.9609375
] |
Sepsis management involved treating elevated inflammatory markers with broad-spectrum antibiotics (Table 1 ), despite negative blood cultures. The antibiotics were initially started at admission to the NICU due to the generalized sickness level of the baby, even though the initial absolute neutrophil count (ANC) was not low and CRP was normal. This was a precautionary measure due to the severe clinical presentation, including generalized hypotonia and bulging open anterior fontanelle. On day five, with CRP being elevated, the sepsis management continued with broad-spectrum antibiotics, leading to the normalization of inflammatory markers and resolution of clinical signs of sepsis. Meningitis was ruled out via lumbar puncture.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p8
|
PMC11277181
|
sec[1]/p[6]
|
Case presentation
| 4.035156 |
clinical
|
Clinical case
|
[
0.336181640625,
0.662109375,
0.0019292831420898438
] |
[
0.051025390625,
0.038360595703125,
0.00443267822265625,
0.90625
] |
On the third day after birth, the infant’s hyperbilirubinemia reached its highest level, with total serum bilirubin (TSB) levels peaking at approximately 10-12 mg/dL (171-205 µmol/L). Effective management with phototherapy was initiated, as this value exceeded the cut-off for a premature infant (35-37 weeks gestation). The total duration of phototherapy was six days. The maximum TSB value recorded was 14.5 mg/dL. This treatment resulted in a gradual reduction of bilirubin levels. To ensure the infant’s well-being, bilirubin levels continued to be carefully monitored following the phototherapy treatment to prevent any rebound hyperbilirubinemia. Apart from suspected sepsis, risk factors for hyperbilirubinemia included prematurity and potential genetic predispositions.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p9
|
PMC11277181
|
sec[1]/p[7]
|
Case presentation
| 4.152344 |
clinical
|
Clinical case
|
[
0.3798828125,
0.6181640625,
0.00203704833984375
] |
[
0.038055419921875,
0.01849365234375,
0.00656890869140625,
0.93701171875
] |
The cardiac assessment uncovered a spectrum of anomalies. Notably, there was a patent foramen ovale with a left-to-right shunt and left ventricular hypertrophy of the non-obstructive variety. Additionally, a moderate tricuspid valve regurgitation was measured at 60 mmHg, alongside a small muscular ventricular septal defect. A significant finding was a large patent ductus arteriosus (PDA), measuring 5 mm with a bidirectional shunt, which fortunately demonstrated considerable improvement over time. The shunt direction was predominantly left-to-right as it became more restrictive with a maximum gradient of approximately 20 mmHg. The left atrium (LA) ratio and superior mesenteric artery (SMA) Doppler were not specified, and no features indicated hemodynamic compromise. These cardiac abnormalities were managed with a conservative approach, showing no indications of heart failure. Despite requiring heightened respiratory support to HFO due to severe respiratory distress, the PDA was managed conservatively because of features suggestive of PPHN, where maintaining a PDA can be beneficial.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p10
|
PMC11277181
|
sec[1]/p[8]
|
Case presentation
| 4.011719 |
clinical
|
Clinical case
|
[
0.339111328125,
0.65869140625,
0.0019092559814453125
] |
[
0.0301513671875,
0.01336669921875,
0.004451751708984375,
0.9521484375
] |
The abdominal ultrasound brought to light a series of renal abnormalities. Among these was a left-sided multicystic dysplastic kidney, accompanied by bilateral hydronephrosis. The left ureter appeared tortuous and dilated, extending all the way to the ureterovesical junction, which was associated with a grade 4 vesicoureteral reflux (VUR). On the other hand, the right ureter showed mild changes consistent with grade 2 VUR. These findings are corroborated by a voiding cystourethrogram. Additionally, there was a suggestion of a duplicated collecting system on the left side. Initial renal function tests indicated elevated creatinine levels, but these levels showed improvement over time (Table 1 ). As a preventive measure, prophylactic antibiotics were prescribed.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p11
|
PMC11277181
|
sec[1]/p[9]
|
Case presentation
| 2.630859 |
clinical
|
Clinical case
|
[
0.056304931640625,
0.93798828125,
0.005889892578125
] |
[
0.0023212432861328125,
0.030426025390625,
0.00213623046875,
0.96533203125
] |
In the first few days, the infant’s nourishment was carefully managed without oral feeding, progressing cautiously to bottle feeding. Initially, the baby faced challenges due to a weak sucking reflex and the presence of thick saliva. To ensure proper nutrition, breast milk was administered through a feeding tube, with the quantity gradually increased over time. As the baby approached discharge, he had developed the ability to feed normally, demonstrated healthy weight gain, and showed excellent tolerance for feeding. Additional nutritional support and guidance for breastfeeding were provided, fostering the baby’s continued growth and development.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p12
|
PMC11277181
|
sec[1]/p[10]
|
Case presentation
| 3.166016 |
clinical
|
Clinical case
|
[
0.1754150390625,
0.81982421875,
0.00479888916015625
] |
[
0.0032711029052734375,
0.00789642333984375,
0.0022144317626953125,
0.98681640625
] |
During the patient's hospitalization, multiple clinical signs raised suspicions of WS, as the patient exhibited several distinctive facial features. These included dystopia canthorum, telecanthus, a striking white forelock, and a notably broad nasal root and bridge. A thorough examination revealed no signs of organomegaly. The patient's male genitalia were within normal parameters, and no skeletal abnormalities were detected. In light of this presentation, a series of tests were recommended, including chromosomal analysis, genetic screening, and hearing evaluations.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p13
|
PMC11277181
|
sec[1]/p[11]
|
Case presentation
| 3.115234 |
clinical
|
Clinical case
|
[
0.3916015625,
0.60400390625,
0.004314422607421875
] |
[
0.00872802734375,
0.0121612548828125,
0.0021114349365234375,
0.97705078125
] |
Upon conducting an auditory brainstem response test, the infant was diagnosed with bilateral sensorineural hearing loss. The infant exhibited neither abnormal movements nor signs of seizures. Additional neurological examinations and brain ultrasound scans were conducted, all of which returned normal findings with no evidence of ventriculomegaly, intraventricular hemorrhage, or structural anomalies.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p14
|
PMC11277181
|
sec[1]/p[12]
|
Case presentation
| 4.117188 |
biomedical
|
Study
|
[
0.9814453125,
0.0183563232421875,
0.0003809928894042969
] |
[
0.8017578125,
0.03631591796875,
0.004322052001953125,
0.1578369140625
] |
The diagnosis of WS in the patient’s father, coupled with the distinctive white forelock observed in four cousins, led to a comprehensive genetic investigation. The recurring appearance of this trait within the family pointed to a strong genetic predisposition, suggesting the likelihood of an inherited disorder. Detailed genetic testing yielded a heterozygous mutation in the PAX3 gene on chromosome 2q36 (Online Mendelian Inheritance in Man (OMIM): 606597). This particular genetic variation is characteristic of WS type 1, which aligns with the phenotypic patterns documented among the relatives.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277181_p15
|
PMC11277181
|
sec[1]/p[13]
|
Case presentation
| 1.331055 |
clinical
|
Clinical case
|
[
0.0214996337890625,
0.96728515625,
0.01125335693359375
] |
[
0.007167816162109375,
0.46142578125,
0.004241943359375,
0.52685546875
] |
Following the patient’s discharge, a scheduled follow-up plan was established, involving regular evaluations by both a urologist and a cardiologist. These consultations are intended to closely monitor the patient’s recuperation and to maintain the highest standard of care for their ongoing health.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p16
|
PMC11277181
|
sec[2]/p[0]
|
Discussion
| 4.261719 |
biomedical
|
Review
|
[
0.99853515625,
0.0014104843139648438,
0.00021457672119140625
] |
[
0.37109375,
0.2154541015625,
0.394287109375,
0.0190887451171875
] |
WS represents a rare cluster of autosomal dominant genetic disorders that embryologically influence the dispersion of melanocytes, resulting in depigmentation across diverse anatomical sites due to the depletion of pigmentary cells in the hair, skin, eyes, and cochlear stria vascularis. Additionally, documented phenotypic presentations encompass a broad nasal root, deaf-mutism, depigmented forelock, aberrantly pigmented iris, hypertrichosed medial eyebrows, and lateral displacement of medial canthi with dystopia of lacrimal puncta .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p17
|
PMC11277181
|
sec[2]/p[1]
|
Discussion
| 4.15625 |
biomedical
|
Study
|
[
0.99951171875,
0.00016701221466064453,
0.0002663135528564453
] |
[
0.935546875,
0.01023101806640625,
0.053680419921875,
0.0003859996795654297
] |
Various types of gene mutations contribute to the onset of WS, including frameshifts, deletions, insertions, missense, and nonsense mutations. Four distinct types of WS have been delineated, with the initial two types being the most prevalent, while the third is exceptionally rare. Classification of these types is based on the specific mutated gene; notably, type 1 arises from a mutation in the PAX3 gene, situated within the 2q36.1 region .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277181_p18
|
PMC11277181
|
sec[2]/p[2]
|
Discussion
| 2.298828 |
biomedical
|
Clinical case
|
[
0.626953125,
0.365966796875,
0.00707244873046875
] |
[
0.017303466796875,
0.0841064453125,
0.0020198822021484375,
0.896484375
] |
Our patient was suspected to have WS type 1 due to the presence of characteristic features (the second, fourth, and fifth major criteria in addition to the third minor criterion) that align with the diagnostic criteria outlined in Table 2 .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277181_p19
|
PMC11277181
|
sec[2]/p[3]
|
Discussion
| 4.015625 |
biomedical
|
Study
|
[
0.9990234375,
0.0007977485656738281,
0.00019288063049316406
] |
[
0.5068359375,
0.332763671875,
0.156005859375,
0.004650115966796875
] |
The diagnosis of WS is confirmed if the patient satisfies either two major criteria or one major criterion along with two minor criteria, or upon detection of a heterozygous pathogenic variant in PAX3 . Additionally, although rare, other reported manifestations of WS encompass cleft lip and/or palate, broad square jaw, low anterior hairline, spina bifida, limb defects, Hirschsprung disease, Sprengel anomaly, and abnormalities of vestibular function .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277181_p20
|
PMC11277181
|
sec[2]/p[4]
|
Discussion
| 2.923828 |
biomedical
|
Other
|
[
0.97607421875,
0.02178955078125,
0.0022335052490234375
] |
[
0.0020465850830078125,
0.9892578125,
0.00440216064453125,
0.004512786865234375
] |
There is no definitive treatment for WS; however, management primarily aims to enhance the patient’s quality of life by addressing some of the abnormal manifestations. Early recognition and treatment of hearing abnormalities are crucial for normal mental development, with cochlear implantation being a definitive intervention. Protection from ultraviolet rays is important for the hypopigmented areas that are easily sun-damaged. Additionally, genetic counseling is a critical aspect to discuss with the family .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p21
|
PMC11277181
|
sec[2]/p[5]
|
Discussion
| 2.542969 |
biomedical
|
Other
|
[
0.99755859375,
0.0012884140014648438,
0.0009098052978515625
] |
[
0.0228271484375,
0.96337890625,
0.01081085205078125,
0.00273895263671875
] |
Children with WS have a normal life expectancy. However, neural-crest-derived tissue-related defects are the main causes of morbidity, which include psychiatric and mental disabilities, skeletal anomalies, ocular disorders, and hearing abnormalities .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p22
|
PMC11277181
|
sec[2]/p[6]
|
Discussion
| 3.699219 |
biomedical
|
Study
|
[
0.978515625,
0.0209808349609375,
0.0004029273986816406
] |
[
0.458984375,
0.141845703125,
0.010040283203125,
0.38916015625
] |
Cardiac and renal manifestations are extremely unlikely to be associated with WS. To our knowledge, two cases of WS have been reported with cardiac anomalies, and only four cases in the literature have been found to have renal anomalies. Among these, two cases had multicystic dysplastic kidney and hydronephrosis, which are similar renal findings to our case. Other reported renal anomalies include duplicated ureteral collecting system and horseshoe kidneys .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277181_p23
|
PMC11277181
|
sec[2]/p[7]
|
Discussion
| 4.089844 |
biomedical
|
Study
|
[
0.99951171875,
0.0001373291015625,
0.00016999244689941406
] |
[
0.982421875,
0.002002716064453125,
0.015472412109375,
0.00017917156219482422
] |
A plausible theory regarding the potential association between WS and renal anomalies suggests that neural crest cells migrate to the embryonic kidney during urinary system development, where they form nephrogenic mesenchyme. This mesenchyme then triggers the differentiation and formation of the kidney . While congenital kidney malformations can arise from aberrant neural crest cell migration, as demonstrated in prior studies, it remains to be thoroughly investigated whether renal abnormalities serve as symptoms of WS .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277181_p24
|
PMC11277181
|
sec[2]/p[8]
|
Discussion
| 3.835938 |
biomedical
|
Other
|
[
0.94482421875,
0.05340576171875,
0.0017070770263671875
] |
[
0.00884246826171875,
0.95166015625,
0.0318603515625,
0.0074462890625
] |
The management of renal issues in patients with WS varies depending on the specific anomalies present. For instance, a duplicated collecting system typically necessitates no treatment unless it is concomitant with another anomaly such as ureteropelvic junction obstruction or VUR . Conversely, patients with a multicystic dysplastic kidney typically require nephrectomy, which is the treatment of choice for this condition . The management of VUR spans from continuous antibiotic prophylaxis to various types of urological surgeries .
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11277181_p25
|
PMC11277181
|
sec[3]/p[0]
|
Conclusions
| 3.660156 |
biomedical
|
Clinical case
|
[
0.74951171875,
0.2486572265625,
0.0017833709716796875
] |
[
0.0234527587890625,
0.148681640625,
0.00789642333984375,
0.81982421875
] |
Finally, we highlight the intricate management of a newborn diagnosed with WS type 1, emphasizing the necessity for a thorough and interdisciplinary approach to complex genetic conditions. The infant exhibited hallmark symptoms of WS, along with unanticipated renal and cardiac abnormalities, which called for meticulous neonatal care and genetic evaluation.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277181_p26
|
PMC11277181
|
sec[3]/p[1]
|
Conclusions
| 3.398438 |
clinical
|
Clinical case
|
[
0.1961669921875,
0.7998046875,
0.00386810302734375
] |
[
0.003734588623046875,
0.036773681640625,
0.0028972625732421875,
0.95654296875
] |
Prompt and effective treatment of critical conditions, including transient tachypnea and hyperbilirubinemia, as well as specialized management of renal and cardiac complications, highlighted the significance of prompt and ongoing care. Furthermore, this case accentuated the vital importance of addressing early hearing impairment and providing genetic counseling to the family, reinforcing the need for early detection and comprehensive care strategies.
|
[
"Ameer Awashra",
"Ahmad Nouri",
"Thabet Zidan",
"Abdelrahman Sawalma",
"Fathi S Milhem",
"Dalia Marbo’"
] |
https://doi.org/10.7759/cureus.63206
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p0
|
PMC11277193
|
sec[0]/p[0]
|
1. Introduction
| 3.8125 |
biomedical
|
Review
|
[
0.99560546875,
0.003101348876953125,
0.001392364501953125
] |
[
0.01099395751953125,
0.1416015625,
0.84521484375,
0.0023593902587890625
] |
The medical treatment of IBD, Crohn’s disease (CD) and ulcerative colitis (UC) was traditionally based on conventional drugs, including 5-aminosalicylates (5-ASAs), corticosteroids and immunomodulators . The availability of biologics, two decades ago, and more recently of small molecules, changed the therapeutic scenario, offering new effective therapeutic tools.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p1
|
PMC11277193
|
sec[0]/p[1]
|
1. Introduction
| 4.070313 |
biomedical
|
Review
|
[
0.998046875,
0.0010938644409179688,
0.0006365776062011719
] |
[
0.147705078125,
0.0027294158935546875,
0.84912109375,
0.00054168701171875
] |
5-ASA and Salazopyrin (SASP) are moderately effective in inducing and maintaining remission in UC , but not in CD . Thiopurines (Azathioprine and 6-Mercaptopurine) and methotrexate proved useful in IBD but their utilization as monotherapy declined following the introduction of biologics. Thiopurines, but not methotrexate , are presently used in association with biological therapies to reduce immunogenicity and secondary loss of response . The association of Azathioprine and anti-tumor necrosis factor α (TNFα) indeed is more effective than anti-TNFα alone in UC , and CD (relative risk (RR) 1.23, 95% confidence interval (CI) 1.02–1.47) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p2
|
PMC11277193
|
sec[0]/p[2]
|
1. Introduction
| 3.876953 |
biomedical
|
Review
|
[
0.99853515625,
0.0010585784912109375,
0.0005970001220703125
] |
[
0.10198974609375,
0.0191497802734375,
0.8779296875,
0.0008606910705566406
] |
The introduction of anti-TNFα , and other biologic agents, including anti-integrins, anti-interleukins and small molecule therapy (Tofacitinib (TOF), Filgotinib and Upadacitinib (UPA)) provided effective additional therapeutic options . Their efficacy was confirmed by the significant decline in overall emergency surgery rates at 5 years , although results were less impressive in severe, complicated UC .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p3
|
PMC11277193
|
sec[0]/p[3]
|
1. Introduction
| 4.128906 |
biomedical
|
Review
|
[
0.994140625,
0.004001617431640625,
0.0018033981323242188
] |
[
0.0128936767578125,
0.0015096664428710938,
0.98486328125,
0.0006270408630371094
] |
Biologics, however, do not represent the golden bullet because approximately one-third of biologic-naïve patients do not respond to anti-TNFα induction and in up to 45% of cases, efficacy is lost over time . A high rate of primary or secondary loss of response is also observed with all other biologics. The choice of escape strategies is thus of prime importance. The present narrative review has been focused on the therapeutic approach in patients undergoing inadequate response and loss of response following induction with ustekinumab (UST), a fully human monoclonal antibody targeting the p40 subunit of interleukin-12 and interleukin-23 . IL-12 and IL-23 are secreted by activated antigen-presenting cells and induce inflammatory and immune functions including natural killer cells activation, CD4+ T-cells differentiation into the T-helper 1 and T-helper 17 induction. UST prevents IL-12 and IL-23 interaction with the surface IL-12Rb1 receptor complexes, thus reducing immune cell activation .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p4
|
PMC11277193
|
sec[0]/p[4]
|
1. Introduction
| 3.935547 |
biomedical
|
Other
|
[
0.97705078125,
0.022125244140625,
0.0008001327514648438
] |
[
0.1578369140625,
0.7392578125,
0.09857177734375,
0.004302978515625
] |
The suggested treatment schedule of UST consists of a single intravenous infusion at the dose of 6 µg/kg body weight, followed by subcutaneous (SC) 90 µg injections every 12 or 8 weeks (q12w–q8w). Available data suggest that about one-fourth of CD and UC patients are primary nonresponders, and loss of response must be expected at a rate of 20% per patient/year. Thus, before deciding to move to other classes of biologics, dose optimization, or reinduction, must be considered.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p5
|
PMC11277193
|
sec[0]/p[5]
|
1. Introduction
| 3.609375 |
biomedical
|
Study
|
[
0.9892578125,
0.0099945068359375,
0.0007138252258300781
] |
[
0.98291015625,
0.0118255615234375,
0.00421905517578125,
0.000988006591796875
] |
Despite being common in clinical practice, UST dose escalation and reinduction in CD and UC patients are not listed in the drug information leaflet. This paper focuses on the off-label use of UST, and analyzes the efficacy of reinduction or dose escalation in primary nonresponders and patients with secondary loss of response to favor effective clinical decision making.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p6
|
PMC11277193
|
sec[1]/p[0]
|
2. Materials and Methods
| 3.931641 |
biomedical
|
Study
|
[
0.99951171875,
0.00028514862060546875,
0.0002295970916748047
] |
[
0.978515625,
0.0013208389282226562,
0.0200042724609375,
0.00020706653594970703
] |
A systematic electronic search of the English literature was performed up to November 2023, using Medline (PubMed), Web of Science, Scopus and the Cochrane Library. The search included a combination of Medical Subject headings (MeSH) and keywords: “IBD”, “Inflammatory Bowel Disease”, “Crohn”, “ulcerative colitis”, “inflammation”, “cytokines”, “immune system”, “biologic therapy” and “Ustekinumab”. Conference proceedings were also screened.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p7
|
PMC11277193
|
sec[1]/p[1]
|
2. Materials and Methods
| 3.330078 |
biomedical
|
Review
|
[
0.98193359375,
0.0036907196044921875,
0.01416015625
] |
[
0.02056884765625,
0.0059814453125,
0.97265625,
0.0005574226379394531
] |
Two authors (F.V.; S.M.) identified relevant articles by screening the abstracts. Additional studies were selected after a manual review of the reference list of the identified studies and review articles. Any discrepancy was resolved by consensus, referring to the original articles. Out of 659 citations, 80 relevant articles were selected and included in the present narrative review.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p8
|
PMC11277193
|
sec[2]/sec[0]/p[0]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 3.371094 |
biomedical
|
Study
|
[
0.9951171875,
0.004192352294921875,
0.0006718635559082031
] |
[
0.94970703125,
0.04705810546875,
0.0022411346435546875,
0.00107574462890625
] |
Three double-blinded multicentric randomized studies (UNITI 1, UNITI 2, IM UNITI) first evaluated the efficacy and safety of ustekinumab in CD .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p9
|
PMC11277193
|
sec[2]/sec[0]/p[1]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 3.90625 |
biomedical
|
Study
|
[
0.90576171875,
0.0916748046875,
0.00237274169921875
] |
[
0.51025390625,
0.48193359375,
0.0032100677490234375,
0.004772186279296875
] |
The induction trials, UNITI-1 and UNITI-2, randomly assigned patients with moderate-to-severe active CD to the following three treatment arms: UST 130 mg, UST 6 mg per kilogram of body weight or placebo . The UNITI-1 trial included 741 patients who did not respond or lost response to anti-TNFα, or experienced side effects to these drugs. The UNITI-2 trial included 628 patients who failed to achieve remission with conventional therapy; they could have previously received one or more TNF antagonists.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p10
|
PMC11277193
|
sec[2]/sec[0]/p[2]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 4.140625 |
biomedical
|
Study
|
[
0.99365234375,
0.0058746337890625,
0.00041413307189941406
] |
[
0.99365234375,
0.00531005859375,
0.0006070137023925781,
0.0003333091735839844
] |
Both UNITI-1 and UNITI-2 showed significantly higher rates of clinical response after 6 weeks in CD patients receiving a single intravenous dose of UST compared with placebo (UNITI-1: 34.3% for UST 130 mg, 33.7% for UST 6 mg per kilogram and 21.5% for placebo, p ≤ 0.003 for both therapeutic regimens vs. placebo; in UNITI-2: 51.7% for UST 130 mg, 55.5% for UST 6 mg per kilogram and 28.7% placebo, p < 0.001 for both therapeutic regimens vs. placebo).
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p11
|
PMC11277193
|
sec[2]/sec[0]/p[3]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 3.689453 |
biomedical
|
Study
|
[
0.9267578125,
0.07080078125,
0.002658843994140625
] |
[
0.82373046875,
0.17138671875,
0.002017974853515625,
0.002880096435546875
] |
All major and minor secondary endpoints, including the reduction in C-reactive protein (CRP) or fecal calprotectin (FC) levels, documented a significant advantage of the two UST-treated groups compared to placebo.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p12
|
PMC11277193
|
sec[2]/sec[0]/p[4]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 4.054688 |
biomedical
|
Other
|
[
0.84716796875,
0.1490478515625,
0.00363922119140625
] |
[
0.431396484375,
0.5576171875,
0.0032520294189453125,
0.0078582763671875
] |
The maintenance study, IM-UNITI, involved 388 responders to induction trials UNITI-1 and UNITI-2, randomly assigned to SC UST, 90 mg every 12 or 8 weeks versus placebo, for 44 weeks . The primary endpoint was clinical remission at week 44 (Crohn’s disease activity index, CDAI score < 150). The major secondary endpoints at week 44 were clinical response (defined as a reduction from baseline in the CDAI score of greater than or equal to 100 points) and steroid-free remission. The trial documented the efficacy of SC maintenance treatment, every 8 or 12 weeks, versus placebo in maintaining clinical response at week 44. Efficacy and exposure–response data favored the administration every 8 weeks compared to every 12 weeks.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p13
|
PMC11277193
|
sec[2]/sec[0]/p[5]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 4.003906 |
biomedical
|
Study
|
[
0.9482421875,
0.050384521484375,
0.0015087127685546875
] |
[
0.85205078125,
0.14306640625,
0.002063751220703125,
0.0026493072509765625
] |
Patients who responded to SC therapy were subsequently included in a long-term extension trial, which showed that SC UST was well tolerated and proved effective in maintaining clinical remission through 5 years (61.9% for patients q12w and 69.5% for q8w). Long-term safety profile and immunogenicity were also encouraging, and similar to those observed in induction and maintenance trials.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p14
|
PMC11277193
|
sec[2]/sec[0]/p[6]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 3.898438 |
biomedical
|
Study
|
[
0.99951171875,
0.00035834312438964844,
0.00028228759765625
] |
[
0.9765625,
0.001384735107421875,
0.02203369140625,
0.0001971721649169922
] |
A recent metanalysis of 38 observational studies reported pooled clinical remission rates for CD of 34% after the induction and 31% at 1 year .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p15
|
PMC11277193
|
sec[2]/sec[0]/p[7]
|
3.1. Ustekinumab, Registrative Trials and Treatment in Naïve CD Patients
| 4.117188 |
biomedical
|
Study
|
[
0.9970703125,
0.0027065277099609375,
0.000324249267578125
] |
[
0.99560546875,
0.00354766845703125,
0.0007977485656738281,
0.0002467632293701172
] |
Limited data concern the efficacy of UST for the treatment of extraintestinal manifestations (EIMs). A post hoc analysis of UNITI-1/2 and IM-UNITI suggested that UST was not superior to placebo in inducing a remission rate of EIMS at weeks 6 and 52 (36.9% UST and 39.1% placebo, p = 0.564 after 6 weeks; 76.4% UST vs. placebo 80%, p = 0.524 after 52 w) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p16
|
PMC11277193
|
sec[2]/sec[1]/p[0]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.164063 |
biomedical
|
Study
|
[
0.98095703125,
0.018463134765625,
0.0005555152893066406
] |
[
0.9755859375,
0.0215606689453125,
0.0016050338745117188,
0.0012493133544921875
] |
A post hoc analysis of two clinical trials (CT-P13 study and UNITI-2 study) compared the efficacy of induction with infliximab (IFX) versus UST in 420 moderate-to-severe, biologic-naïve, CD patients, with comparable results. Clinical remission with IFX or UST at week 6 were 44.9% and 37.9%, respectively. The clinical response rate at week 6 was about the same (58.4% vs. 54.9%) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p17
|
PMC11277193
|
sec[2]/sec[1]/p[1]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.167969 |
biomedical
|
Study
|
[
0.998046875,
0.00183868408203125,
0.0002238750457763672
] |
[
0.998046875,
0.0010690689086914062,
0.0008068084716796875,
0.00020503997802734375
] |
A comprehensive comparison of UST or adalimumab (ADA) in the United States has been provided by a large real-world retrospective study in biologic-naïve CD patients. Five thousand ninety-one CD patients were enrolled . After 14.9 months follow-up in the UST cohort and 16.9 months in the ADA cohort, UST had a 50% higher rate of treatment persistence compared to ADA (HR: 1.50; 95% CI: 1.29–1.74; p -value < 0.001). The UST cohort had a 17% higher rate of corticosteroid-free remission compared to ADA (HR: 1.17; 95% CI; 1.04–1.31; p -value = 0.008). Within 12 months of maintenance, 11.2% of patients in the UST- and 16.9% of the ADA-treated cohort required dose escalation. These findings suggested that UST could represent an effective first-line treatment in CD .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p18
|
PMC11277193
|
sec[2]/sec[1]/p[2]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.101563 |
biomedical
|
Study
|
[
0.9912109375,
0.008331298828125,
0.0006222724914550781
] |
[
0.98193359375,
0.016082763671875,
0.0013055801391601562,
0.0005164146423339844
] |
Conversely, the SEAVUE trial, including 386 naïve CD patients randomly assigned to UST or ADA, after 1 year of follow-up could not document significant differences in efficacy (clinical remission: 65% UST vs. 61% ADA, p = 0.4) and safety (severe infections: 2% UST vs. 3% ADA .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p19
|
PMC11277193
|
sec[2]/sec[1]/p[3]
|
3.2. Ustekinumab versus Other Therapies in CD
| 3.75 |
biomedical
|
Study
|
[
0.9990234375,
0.0006093978881835938,
0.0002682209014892578
] |
[
0.998046875,
0.0012607574462890625,
0.0007128715515136719,
0.00013625621795654297
] |
A retrospective study based on the Korean National Database analyzing treatment persistence in 2987 CD patients who were starting biologics suggested that UST is superior to anti-TNFα in bio-naïve subjects .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11277193_p20
|
PMC11277193
|
sec[2]/sec[1]/p[4]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.132813 |
biomedical
|
Study
|
[
0.998046875,
0.0014715194702148438,
0.00030493736267089844
] |
[
0.99853515625,
0.0008497238159179688,
0.0005249977111816406,
0.00011217594146728516
] |
Moreover, in a smaller study (97 ADA and 66 UST), the clinical response rate (73.2% vs. 50%, p < 0.02) and the remission rate (44.3% vs. 27.7%, p < 0.032 at 16 weeks) were higher in the ADA group. A nonsignificant trend favoring UST in the clinical response rate (52% vs. 25%, p < 0.24) and the clinical remission rate (25% vs. 27%, p < 0.82) was observed, as expected, in the subgroup of anti-TNFα–experienced patients .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p21
|
PMC11277193
|
sec[2]/sec[1]/p[5]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.15625 |
biomedical
|
Study
|
[
0.982421875,
0.0169830322265625,
0.0005092620849609375
] |
[
0.99462890625,
0.003719329833984375,
0.001132965087890625,
0.0007300376892089844
] |
The efficacy of UST versus a second anti-TNFα agent in anti-TNFα–experienced patients was evaluated in a retrospective cohort. Treatment persistence at 3 years were similar (35% of UST vs. 36% of anti-TNFα, p = 0.72). No significant difference was observed in the 3-year hospital admission rate (28% vs. 30%, p = 0.99), infection-related hospital admission (8% vs. 8%, p = 0.31), surgery (13% vs. 8%, p = 0.17) and a need for antibiotics (51% vs. 50%, p = 0.56). The proportion of patients still using the second-line therapy was not influenced by the first-line anti-TNFα (ADA or IFX) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p22
|
PMC11277193
|
sec[2]/sec[1]/p[6]
|
3.2. Ustekinumab versus Other Therapies in CD
| 3.792969 |
biomedical
|
Study
|
[
0.98876953125,
0.010711669921875,
0.0005946159362792969
] |
[
0.99365234375,
0.00418853759765625,
0.0014448165893554688,
0.0006070137023925781
] |
Instead, no difference in clinical remission rates was observed between anti-TNFα and UST (48.3% vs. 56%, p = 0.8) as second-line biological therapy after VDZ failure .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11277193_p23
|
PMC11277193
|
sec[2]/sec[1]/p[7]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.15625 |
biomedical
|
Study
|
[
0.9990234375,
0.0009655952453613281,
0.00022804737091064453
] |
[
0.99853515625,
0.0004978179931640625,
0.0009737014770507812,
0.00011986494064331055
] |
UST and Vedolizumab (VDZ) were compared in a cohort of 470 anti-TNFα–experienced CD patients . Similar clinical remission rates were reported at 26 weeks (UST 60.1% vs. VDZ 65.4%, p = 0.277), but VDZ was associated with higher remission rates at 1 year (55.5% vs. 42.5% UST, p = 0.038). Conversely, in a study carried out in anti-TNFα–experienced CD patients (107 UST and 132 VDZ), UST proved more effective at week 48 in inducing clinical remission (54.4% vs. 38.3%; odds ratio (OR) = 1.92, 95% CI [1.09–3.39]), more so in ileal and penetrating disease. Treatment persistence was also better in the UST arm (71.5% vs. 49.7%; OR = 2.54, 95% CI [1.40–4.62], but not the steroid-free clinical remission rate (44.7% vs. 34.0%; OR = 1.57, 95% CI [0.88–2.79]) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p24
|
PMC11277193
|
sec[2]/sec[1]/p[8]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.152344 |
biomedical
|
Study
|
[
0.99609375,
0.003444671630859375,
0.00027823448181152344
] |
[
0.99755859375,
0.0014524459838867188,
0.0008091926574707031,
0.0002586841583251953
] |
Following the failure an anti-TNF agent in 203 CD patients, UST, VDZ or a second anti-TNF agent showed similar steroid-free remission rates (29%, 38% and 44%, respectively, p = 0.15) at weeks 14 and 24. After a mean follow-up of 118 weeks (±93), the drug persistence was shorter in patients who received UST ( p = 0.001) . A smaller cohort confirmed these results . The clinical remission rates were similar in UST- and VDZ-treated patients (CDAI < 150, 50.0% vs. 53.6%, p = 0.820) as well as sustained clinical response at week 48 ( p = 0.692) and safety profiles. Nonetheless, the size of these cohorts prevents definitive conclusions.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p25
|
PMC11277193
|
sec[2]/sec[1]/p[9]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.15625 |
biomedical
|
Study
|
[
0.99365234375,
0.00572967529296875,
0.0004076957702636719
] |
[
0.9892578125,
0.0094757080078125,
0.000736236572265625,
0.0004432201385498047
] |
Recently, UST was compared to guselkumab (GUS) in patients completing the 48-week maintenance therapy with GUS in the GALAXI-1 long-term extension (LTE) study. As expected for long-term responders, endoscopic response at week 144, defined as ≥50% improvement from baseline in the simple endoscopic score for CD (SES-CD) or SES-CD ≤ 2, was superior in the GUS arm as compared to UST (34.7% vs. 19.4%) . However, a post hoc analysis of the same trial suggested a higher endoscopic response compared to UST also in patients who did not achieve a 12-week clinical response (31.7% and 23.8%, respectively) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p26
|
PMC11277193
|
sec[2]/sec[1]/p[10]
|
3.2. Ustekinumab versus Other Therapies in CD
| 3.646484 |
biomedical
|
Study
|
[
0.98876953125,
0.0101470947265625,
0.001194000244140625
] |
[
0.990234375,
0.00862884521484375,
0.000911712646484375,
0.0004425048828125
] |
The efficacy of UST was also compared with Risankizumab, with the latter showing higher rates of endoscopic remission at week 48 (16.2% vs. 31.8%) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p27
|
PMC11277193
|
sec[2]/sec[1]/p[11]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.128906 |
biomedical
|
Study
|
[
0.9990234375,
0.0009694099426269531,
0.00017452239990234375
] |
[
0.9990234375,
0.0004661083221435547,
0.00058746337890625,
0.0001271963119506836
] |
UST proved superior to azathioprine in preventing endoscopic postoperative recurrence (POR) in a retrospective study involving 63 CD patients. Endoscopic POR (Rutgeerts’ index ≥ i2) and severe endoscopic POR (Rutgeerts’ index ≥ i3) were 20.8% versus 42.5% ( p = 0.066) and 16.9% versus 27.9% ( p = 0.24) following UST and azathioprine, respectively .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p28
|
PMC11277193
|
sec[2]/sec[1]/p[12]
|
3.2. Ustekinumab versus Other Therapies in CD
| 3.992188 |
biomedical
|
Study
|
[
0.998046875,
0.0018758773803710938,
0.00032067298889160156
] |
[
0.99853515625,
0.0011348724365234375,
0.0002989768981933594,
0.00017273426055908203
] |
A similar risk of overall postoperative complications was observed in 30 CD patients treated with UST and 73 with VDZ at week 12 (OR 95% CI 0.38 (0.10–1.4); p = 0.15) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p29
|
PMC11277193
|
sec[2]/sec[1]/p[13]
|
3.2. Ustekinumab versus Other Therapies in CD
| 4.054688 |
biomedical
|
Study
|
[
0.99609375,
0.0035228729248046875,
0.0003712177276611328
] |
[
0.99853515625,
0.0007386207580566406,
0.0005106925964355469,
0.0002015829086303711
] |
Endoscopic recurrence rates within a year following surgery (Rutgeerts score ≥ i2) were also compared in patients undergoing ADA or UST. Despite UST patients being older, having longer disease duration and being exposed to more biologics, endoscopic recurrence rates were nonsignificantly higher (58.3% vs. 47.6%, p = 0.3) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p30
|
PMC11277193
|
sec[2]/sec[2]/p[0]
|
3.3. Dose Escalation and Reinduction in CD
| 2.486328 |
biomedical
|
Other
|
[
0.99365234375,
0.004146575927734375,
0.0020694732666015625
] |
[
0.355224609375,
0.51953125,
0.12109375,
0.004413604736328125
] |
Like with other biologics, a proportion of patients experience primary or secondary nonresponse to UST, and dose escalation has been considered. Despite the wide use of UST in clinical practice, relatively few data are available on dose optimization or reinduction in this subset of patients.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p31
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[0]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 2.298828 |
biomedical
|
Study
|
[
0.9794921875,
0.01160430908203125,
0.0087890625
] |
[
0.91015625,
0.08355712890625,
0.004772186279296875,
0.0013475418090820312
] |
As previously reported, the IM-UNITI trial favored the administration every 8 weeks over longer intervals .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p32
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[1]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 4.164063 |
biomedical
|
Study
|
[
0.99658203125,
0.003368377685546875,
0.0002903938293457031
] |
[
0.9970703125,
0.0021610260009765625,
0.0006270408630371094,
0.00029277801513671875
] |
Similar results have been reported in a cohort of 139 CD patients allocated to UST maintenance every 8 weeks (85 patients) or 12 weeks (54 patients) . This series included a higher percentage of anti-TNF-α and anti-integrin–exposed patients than the IM-UNITI trial, and may be considered more representative of real-life clinical practice. A shortened administration interval correlated with lower discontinuation rates (20% vs. 42.6%, p = 0.01) at week 52, but not with corticosteroid-free clinical remission (46.3% vs. 34.6%, p = 0.20). Despite similar baseline characteristics, the Harvey–Bradshaw Index (HBI) was significantly higher at week 12 in the q8w-treated group (6 vs. 5, p = 0.04), suggesting that the 8-week interval was preferred in patients with more aggressive disease . This may represent a relevant bias and affect conclusions.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p33
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[2]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 2.541016 |
biomedical
|
Study
|
[
0.99560546875,
0.0009312629699707031,
0.003429412841796875
] |
[
0.9931640625,
0.0048980712890625,
0.0015287399291992188,
0.0001844167709350586
] |
Several studies suggest the opportunity to further shorten the intervals to 6 or 4 weeks ( Table 1 , study design reported in Supplementary Table S1 ) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p34
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[3]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 4.105469 |
biomedical
|
Study
|
[
0.927734375,
0.07135009765625,
0.0008492469787597656
] |
[
0.93896484375,
0.053466796875,
0.002269744873046875,
0.005161285400390625
] |
The drug administration interval was shortened from 8 to 4 weeks in 110 nonresponders out of 506 CD patients after a median time of 7.5 months. Following dose escalation, clinical remission (HBI < 4) was observed in 50.9% of patients, after a median time of 5 months. A reduction in CRP < 5 mg/L and an improvement of FC (FC < 250 μg/g) were observed in 29.1% and 50% of patients, respectively. Endoscopic remission (quiescent disease) was reported in 36% of patients who had baseline moderate-to-severe disease .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p35
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[4]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 4.136719 |
biomedical
|
Study
|
[
0.9990234375,
0.0007991790771484375,
0.0001842975616455078
] |
[
0.9990234375,
0.00046253204345703125,
0.0005097389221191406,
0.0001176595687866211
] |
Similarly, a retrospective observational study proved that a 4-week dose escalation improves clinical symptoms evaluated by the physician global assessment score (PGA) (0.47 ± 0.19, p < 0.05) and reduces CRP (0.33 ± 0.19 mg/L, p < 0.05), but also improves albumin levels (0.23 ± 0.06 g/dL, p < 0.05) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p36
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[5]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 4.164063 |
biomedical
|
Study
|
[
0.998046875,
0.0018205642700195312,
0.00022125244140625
] |
[
0.998046875,
0.0006952285766601562,
0.001155853271484375,
0.0001863241195678711
] |
Dose intensification to 4 and 6 weeks was retrospectively evaluated in 123 patients in a study comparing the efficacy of the two regimens. The study reported that both strategies were clinically effective, because more than 50% of patients in the two groups achieved corticosteroid-free remission at 12 and 24 months. Interestingly enough, more than 80% of CD patients who were in corticosteroid-free remission at week 12 maintained remission at week 24. However, q4w patients had a significantly higher need for systemic corticosteroids (31.3% vs. 14.6%, p = 0.03) and longer CD duration at baseline (15.5 years vs. 12.7, p = 0.08). As in other retrospective studies, q4w patients likely had more severe disease, and the authors concluded that similar efficacy of the two regimens could not be unequivocally supported by their data. As secondary outcomes, the study suggested that, as expected, perianal disease, a higher HBI and use of opioids and corticosteroids were associated with UST failure .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p37
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[6]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 3.939453 |
biomedical
|
Study
|
[
0.99755859375,
0.0023746490478515625,
0.0002741813659667969
] |
[
0.99658203125,
0.0022983551025390625,
0.0008554458618164062,
0.0002989768981933594
] |
Fumery et al. showed that after a median of 2.4 months after dose intensification (4 weeks) clinical response and clinical remission were observed, respectively, in 61% and 31% of patients who lost response to q8w administration .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p38
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[7]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 3.84375 |
biomedical
|
Study
|
[
0.99951171875,
0.00045013427734375,
0.0002219676971435547
] |
[
0.98583984375,
0.001373291015625,
0.012420654296875,
0.0001722574234008789
] |
Other studies in smaller series confirmed that shortening the administration interval from 8 to 4 weeks was effective and safe in regaining response and inducing clinical remission, with the median time varying from 4 weeks to 6 months ( Table 1 ) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p39
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[8]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 3.953125 |
biomedical
|
Study
|
[
0.9833984375,
0.016204833984375,
0.0005397796630859375
] |
[
0.9833984375,
0.01482391357421875,
0.0008344650268554688,
0.0009250640869140625
] |
According to Hanzel, in 44 patients who underwent a 4-week dose escalation, endoscopic remission (SES-CD ≤ 3 without ulceration) was achieved in 28.6%, CRP normalization in 29.2% and FC normalization in 51.7% of patients .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p40
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[9]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 3.988281 |
biomedical
|
Study
|
[
0.94189453125,
0.057281494140625,
0.0009303092956542969
] |
[
0.98046875,
0.0162353515625,
0.0011234283447265625,
0.0021038055419921875
] |
Similarly, UST dose escalation to 90 mg every 4 or 6 weeks led to clinical remission within 3–6 months in 30.9% of the 68 patients. Of the patients with available endoscopic follow-up data (n = 39), 59% had endoscopic response and 20.5% achieved endoscopic remission .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p41
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[10]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 4.070313 |
biomedical
|
Study
|
[
0.9990234375,
0.0006732940673828125,
0.00020647048950195312
] |
[
0.9892578125,
0.00055694580078125,
0.009918212890625,
0.00016427040100097656
] |
Overall, the endoscopic remission rate following a shortened administration interval varied in differing series from 8.6% to 43.4%, and endoscopic improvement was observed in about two-thirds of patients ( Table 1 ) . A recent metanalysis including 126 patients reported endoscopic improvement in 61% (CI 52–69%) of patients and endoscopic remission in 29% (CI 16–44%) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p42
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[11]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 3.230469 |
biomedical
|
Study
|
[
0.99609375,
0.0024547576904296875,
0.001377105712890625
] |
[
0.99609375,
0.0026798248291015625,
0.0009427070617675781,
0.0002346038818359375
] |
The q4w administration was more effective in preventing recurrence compared to the 8-week regimen ( p < 0.05) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p43
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[12]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 1.912109 |
biomedical
|
Study
|
[
0.99267578125,
0.0032978057861328125,
0.004055023193359375
] |
[
0.7490234375,
0.211669921875,
0.03546142578125,
0.003787994384765625
] |
Data on the efficacy of UST dose escalation on perianal disease have been reported in some studies.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p44
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[13]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 3.115234 |
biomedical
|
Study
|
[
0.5185546875,
0.47705078125,
0.00424957275390625
] |
[
0.6826171875,
0.278076171875,
0.0021991729736328125,
0.037017822265625
] |
Twelve out of twenty-four patients with perianal disease included in a series of thirty-eight patients who did not respond to standard UST maintenance and underwent dose escalation to 90 mg every 4 or 6 weeks showed improvement and few patients required surgery .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p45
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[14]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 3.765625 |
biomedical
|
Study
|
[
0.95166015625,
0.04736328125,
0.0011720657348632812
] |
[
0.9765625,
0.0200042724609375,
0.0015535354614257812,
0.0018815994262695312
] |
In another series of 28 patients with perianal disease, 36% achieved clinical remission of perianal fistulas at week 24. No difference was found between the q8w and q12w treatment schedule . Resolution of perianal symptoms was reported in 5 of 11 patients (45%) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p46
|
PMC11277193
|
sec[2]/sec[2]/sec[0]/p[15]
|
3.3.1. Dose Escalation and Shortening the Interval between Doses
| 2.222656 |
biomedical
|
Study
|
[
0.9951171875,
0.0022335052490234375,
0.0026874542236328125
] |
[
0.418701171875,
0.275146484375,
0.3017578125,
0.00452423095703125
] |
These reports are encouraging but no clear-cut conclusions may be drawn because the efficacy of a reduced UST administration interval on perianal disease results from small, retrospective series.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p47
|
PMC11277193
|
sec[2]/sec[2]/sec[1]/p[0]
|
3.3.2. Intravenous Reinduction in CD Patients who Lost Response to UST or with an Unsatisfactory Response to “Conventional” Dose Escalation
| 4.132813 |
biomedical
|
Study
|
[
0.978515625,
0.0206451416015625,
0.0007619857788085938
] |
[
0.9755859375,
0.0219268798828125,
0.001220703125,
0.0012598037719726562
] |
The efficacy and safety of single IV reinduction (6 mg/kg) followed by SC 90 mg UST q8w versus standard 90 mg SC UST q8w was evaluated in 215 CD patients with secondary loss of response to UST 90 mg q8w. A higher proportion of patients from the IV arm achieved clinical response at week 16 (49.1% vs. 37.4%, p = 0.089). Endoscopic remission, FC normalization and IBDQ-score improvement also favored the IV arm (18.6% vs. 5%, p = 0.043; 17% vs. 9%, p = 0.145; 59% vs. 43%, p = 0.017, respectively). It thus appears that a single IV administration significantly improves standard q8w maintenance therapy . Recently, a post hoc analysis of this study suggested that patients with a higher disease burden at baseline (disease extent or elevated inflammatory biomarkers) were more likely to benefit from UST IV reinduction .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p48
|
PMC11277193
|
sec[2]/sec[2]/sec[1]/p[1]
|
3.3.2. Intravenous Reinduction in CD Patients who Lost Response to UST or with an Unsatisfactory Response to “Conventional” Dose Escalation
| 4.15625 |
biomedical
|
Study
|
[
0.97509765625,
0.0242156982421875,
0.0006909370422363281
] |
[
0.98779296875,
0.0101776123046875,
0.0010633468627929688,
0.0011835098266601562
] |
Dose escalation (4 or 6 weeks), intravenous reinduction or a combination of the two were retrospectively compared in a multicenter cohort of 142 CD patients. Ninety-one (64.1%) of the patients were escalated to the q4w regimen, twenty (14.1%) patients were escalated to q6w, fourteen (9.9%) patients received an IV reinduction and seventeen (12%) patients received a combination of IV reinduction and interval shortening. Clinical response at week 16 (ΔHBI ≥ 3 or ΔCDAI ≥ 70) was achieved by 51.4% of patients, CRP normalized in 21.4% of patients and corticosteroid-free remission was achieved by 17.6% of patients on corticosteroids upon escalation. The likelihood of achieving clinical response at week 16 did not statistically differ in patients who received intravenous reinduction versus those who received SC interval shortening (65.8% with q4w, 13.7% with q6w, 13.7% with q4w and 6.8% with IV reinduction, p = 0.48). Thus, nonresponders may benefit from dose escalation, but no differences between SC escalation and IV reinduction were detected .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p49
|
PMC11277193
|
sec[2]/sec[2]/sec[1]/p[2]
|
3.3.2. Intravenous Reinduction in CD Patients who Lost Response to UST or with an Unsatisfactory Response to “Conventional” Dose Escalation
| 1.757813 |
biomedical
|
Study
|
[
0.97314453125,
0.004016876220703125,
0.0229339599609375
] |
[
0.8642578125,
0.11541748046875,
0.0180511474609375,
0.0024509429931640625
] |
Similar results were reported in a smaller study .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p50
|
PMC11277193
|
sec[2]/sec[2]/sec[1]/p[3]
|
3.3.2. Intravenous Reinduction in CD Patients who Lost Response to UST or with an Unsatisfactory Response to “Conventional” Dose Escalation
| 4.195313 |
biomedical
|
Study
|
[
0.99560546875,
0.004245758056640625,
0.00024437904357910156
] |
[
0.99755859375,
0.0016660690307617188,
0.0005884170532226562,
0.00039124488830566406
] |
A multicenter, retrospective cohort study involving 56 CD patients reported the efficacy of IV UST reinduction after a partial response or loss of response on SC UST maintenance. Clinical remission at week 16 was observed in 43.3% of patients undergoing IV reinduction, as well as an improvement in biomarker values (PCR 6.3 ± 7.4 mg/L, p = 0.08; FC 194 ± 154 μg/g, p = 0.22) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p51
|
PMC11277193
|
sec[2]/sec[2]/sec[2]/p[0]
|
3.3.3. IV Ustekinumab at Regular Intervals in CD
| 4.160156 |
biomedical
|
Study
|
[
0.98828125,
0.01125335693359375,
0.0003838539123535156
] |
[
0.99560546875,
0.0028285980224609375,
0.0009255409240722656,
0.0006513595581054688
] |
This issue was addressed in a retrospective study in 79 patients (73 CD and 6 UC) undergoing IV doses every 4–6 weeks following an inadequate response or loss of response to 90 mg SC every 4–6 weeks. Twelve weeks after the first IV dose, 43% of patients were in clinical remission (HBI < 5). The figure increased to 59.5% after a 14-month follow-up. Basal FC significantly decreased at month 12 and at the end of follow-up . Thus, prolonged intravenous maintenance treatment proved effective in a large proportion of patients failing to respond to intensified SC UST .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p52
|
PMC11277193
|
sec[2]/sec[2]/sec[2]/p[1]
|
3.3.3. IV Ustekinumab at Regular Intervals in CD
| 3.126953 |
biomedical
|
Study
|
[
0.99853515625,
0.0008606910705566406,
0.0004096031188964844
] |
[
0.99169921875,
0.006313323974609375,
0.0015268325805664062,
0.00040435791015625
] |
Similarly, a recent small Spanish study confirmed these results, because UST 130 mg every 4 weeks induced clinical and biochemical improvement in 27 CD patients .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p53
|
PMC11277193
|
sec[2]/sec[2]/sec[2]/p[2]
|
3.3.3. IV Ustekinumab at Regular Intervals in CD
| 2.689453 |
biomedical
|
Other
|
[
0.99267578125,
0.005275726318359375,
0.0021533966064453125
] |
[
0.1044921875,
0.67626953125,
0.215576171875,
0.0036907196044921875
] |
While dose escalation and reinduction both improve clinical and endoscopic outcomes in CD, it is still unclear how to identify those patients who will profit from more aggressive therapeutic strategies.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p54
|
PMC11277193
|
sec[2]/sec[2]/sec[2]/p[3]
|
3.3.3. IV Ustekinumab at Regular Intervals in CD
| 4.078125 |
biomedical
|
Study
|
[
0.99951171875,
0.00038361549377441406,
0.00019633769989013672
] |
[
0.99853515625,
0.00027060508728027344,
0.0012941360473632812,
0.00008767843246459961
] |
Baseline CPR was reported by a Finnish nationwide real-world study as the only effective predictor of patients requiring dose intensification . Fistulizing behavior, ≥2 biological failure and lack of steroid-free remission at week 12 after UST induction all predicted poor efficacy of standard dose escalation in an Australian retrospective study . This was well expected because these parameters identify a subset of patients with particularly aggressive and resistant disease. In another study, response to the UST induction dose was the best predictor of subsequent response to UST dose escalation (OR: 7.01; 95% CI 1.83–27.07; p = 0.005) . This, again, could be anticipated.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p55
|
PMC11277193
|
sec[2]/sec[2]/sec[2]/p[4]
|
3.3.3. IV Ustekinumab at Regular Intervals in CD
| 3.9375 |
biomedical
|
Study
|
[
0.73828125,
0.259521484375,
0.002361297607421875
] |
[
0.779296875,
0.199951171875,
0.00279998779296875,
0.01776123046875
] |
Adverse events following escalation were reported in 11 (7.7%) of the 142 patients who underwent dose escalation every 4 or 6 weeks in the Kopylov series. These events were usually mild, consisting of skin eruptions in two patients, acute gastroenteritis of unknown etiology in two patients and one case each of a clostridium difficile infection, CMV colitis, concentration disturbance and a benign breast lump. A few severe adverse events were also reported in the series consisting of cervical intraepithelial neoplasia grade 1, nonmelanoma skin cancer and an upper respiratory tract infection that required hospitalization, one case each .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277193_p56
|
PMC11277193
|
sec[2]/sec[2]/sec[2]/p[5]
|
3.3.3. IV Ustekinumab at Regular Intervals in CD
| 2.636719 |
clinical
|
Other
|
[
0.2034912109375,
0.79150390625,
0.00498199462890625
] |
[
0.395263671875,
0.446044921875,
0.004486083984375,
0.1541748046875
] |
No serious adverse events were reported in 65 patients who underwent UST reinduction. One patient experienced facial erythema and mild dyspnea but completed the infusion at a lower rate .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p57
|
PMC11277193
|
sec[2]/sec[2]/sec[2]/p[6]
|
3.3.3. IV Ustekinumab at Regular Intervals in CD
| 3.351563 |
biomedical
|
Study
|
[
0.99560546875,
0.002857208251953125,
0.0013113021850585938
] |
[
0.57958984375,
0.35888671875,
0.05914306640625,
0.0021266937255859375
] |
Thus, UST dose escalation and reinduction are safe and should be considered before switching out of class. However further studies are required to compare the two strategies and define the optimal therapeutic administration intervals and evaluate long-term safety of these approaches.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p58
|
PMC11277193
|
sec[2]/sec[3]/p[0]
|
3.4. Ustekinumab, Registrative Trials and Treatment in Naïve UC Patients
| 3.992188 |
biomedical
|
Other
|
[
0.69775390625,
0.29638671875,
0.00589752197265625
] |
[
0.2239990234375,
0.76220703125,
0.0031147003173828125,
0.010589599609375
] |
The efficacy and safety of induction and maintenance of UST in patients with moderate-to-severe UC were reported in the UNIFI randomized controlled trial . Nine hundred sixty-one patients were randomly assigned to three induction treatment groups with intravenous UST at the dose of 130 mg or 6 mg/kg body weight, or placebo. Responders to induction therapy at 8 weeks subsequently received subcutaneously maintenance doses of 90 mg UST every 8 or 12 weeks, or placebo .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p59
|
PMC11277193
|
sec[2]/sec[3]/p[1]
|
3.4. Ustekinumab, Registrative Trials and Treatment in Naïve UC Patients
| 4.128906 |
biomedical
|
Study
|
[
0.9697265625,
0.02911376953125,
0.0009636878967285156
] |
[
0.96484375,
0.032196044921875,
0.0015935897827148438,
0.0012874603271484375
] |
At week 8, the clinical remission rate was superior to placebo, but nonetheless unsatisfactory, ranging about 15%. Clinical response and endoscopic improvement (Mayo score of 0 or 1) were significantly higher following the UST 130 mg (51.3% and 26.3%) and UST 6 mg/kg groups (61.8% and 27%) than in the placebo group (31.3% and 13.8%) ( p < 0.001).
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p60
|
PMC11277193
|
sec[2]/sec[3]/p[2]
|
3.4. Ustekinumab, Registrative Trials and Treatment in Naïve UC Patients
| 3.957031 |
biomedical
|
Study
|
[
0.98388671875,
0.01486968994140625,
0.0010471343994140625
] |
[
0.9853515625,
0.0132598876953125,
0.0006957054138183594,
0.000530242919921875
] |
Persistent clinical remission in responders was significantly higher at 44 weeks in the UST-treated patients q12w (38.4%) and q8w (43.8%) than with placebo (24.0%) ( p < 0.002).
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p61
|
PMC11277193
|
sec[2]/sec[3]/p[3]
|
3.4. Ustekinumab, Registrative Trials and Treatment in Naïve UC Patients
| 4.152344 |
biomedical
|
Study
|
[
0.99072265625,
0.0088348388671875,
0.0004723072052001953
] |
[
0.99072265625,
0.0072479248046875,
0.0015363693237304688,
0.0004687309265136719
] |
The same proved true for clinical response in patients receiving UST every 12 weeks, UST every 8 weeks or placebo-favored UST (68%, 71% and 44.6%, for q12w, q8w and placebo), endoscopic improvement (43.6%, 51.1% and 28.6%, respectively p < 0.001) and corticosteroid-free clinical remission (37.8%, 42% and 23.4%, p < 0.001).
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p62
|
PMC11277193
|
sec[2]/sec[3]/p[4]
|
3.4. Ustekinumab, Registrative Trials and Treatment in Naïve UC Patients
| 2.693359 |
biomedical
|
Study
|
[
0.99072265625,
0.00626373291015625,
0.0030155181884765625
] |
[
0.9462890625,
0.037841796875,
0.01409149169921875,
0.0018053054809570312
] |
A recent metanalysis reported a postinduction clinical remission rate of 39% .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p63
|
PMC11277193
|
sec[2]/sec[3]/p[5]
|
3.4. Ustekinumab, Registrative Trials and Treatment in Naïve UC Patients
| 2.535156 |
biomedical
|
Study
|
[
0.8837890625,
0.1121826171875,
0.004077911376953125
] |
[
0.83837890625,
0.15185546875,
0.0032138824462890625,
0.006427764892578125
] |
The incidence of adverse events did not differ in UST- and placebo-treated patients, ranging about 45%, but mainly consisting of mild adverse events.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p64
|
PMC11277193
|
sec[2]/sec[3]/p[6]
|
3.4. Ustekinumab, Registrative Trials and Treatment in Naïve UC Patients
| 2.572266 |
biomedical
|
Other
|
[
0.990234375,
0.007450103759765625,
0.0022487640380859375
] |
[
0.11859130859375,
0.86767578125,
0.01055145263671875,
0.0033168792724609375
] |
On the base of these results, UST treatment may be considered for the treatment of patients with moderate-to-severe UC.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p65
|
PMC11277193
|
sec[2]/sec[4]/p[0]
|
3.5. Ustekinumab versus Other Therapies in UC
| 2.691406 |
biomedical
|
Other
|
[
0.9970703125,
0.0010480880737304688,
0.0019207000732421875
] |
[
0.227294921875,
0.45361328125,
0.316162109375,
0.00284576416015625
] |
Head-to-head comparison of different biological drugs or immunosuppressants is essential for precision medicine and a patient-tailored therapeutic approach. Data, however, are scarce and largely derive from indirect comparisons or retrospective studies.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277193_p66
|
PMC11277193
|
sec[2]/sec[4]/p[1]
|
3.5. Ustekinumab versus Other Therapies in UC
| 2.164063 |
biomedical
|
Study
|
[
0.99658203125,
0.0014600753784179688,
0.002201080322265625
] |
[
0.697265625,
0.1478271484375,
0.152099609375,
0.00292205810546875
] |
A relatively small number of studies compared the efficacy of UST versus VDZ or anti-TNFα in UC patients.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p67
|
PMC11277193
|
sec[2]/sec[4]/p[2]
|
3.5. Ustekinumab versus Other Therapies in UC
| 4.082031 |
biomedical
|
Study
|
[
0.9990234375,
0.0005908012390136719,
0.00021219253540039062
] |
[
0.9990234375,
0.0004432201385498047,
0.00035262107849121094,
0.00008779764175415039
] |
A multicentric GETAID cohort study did not find differences between UST and VDZ in terms of steroid-free clinical remission at week 52 in anti-TNFα–exposed patients (OR = 0.55 [0.21–1.41], p = 0.21 and 0.94 [0.40–2.22], p = 0.89) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277193_p68
|
PMC11277193
|
sec[2]/sec[4]/p[3]
|
3.5. Ustekinumab versus Other Therapies in UC
| 4.085938 |
biomedical
|
Study
|
[
0.99462890625,
0.00476837158203125,
0.0004413127899169922
] |
[
0.99609375,
0.0029392242431640625,
0.0006647109985351562,
0.0002942085266113281
] |
Despite no difference was observed in terms of clinical remission, UST showed a higher efficacy in terms of endoscopic remission at week 16 (17.5% vs. 5.3%; OR = 3.77 [1.25–11.36]; p = 0.018) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p69
|
PMC11277193
|
sec[2]/sec[4]/p[4]
|
3.5. Ustekinumab versus Other Therapies in UC
| 4.132813 |
biomedical
|
Study
|
[
0.966796875,
0.03228759765625,
0.0010881423950195312
] |
[
0.970703125,
0.0267486572265625,
0.0010976791381835938,
0.0014009475708007812
] |
UST, anti-TNFα and VDZ were prospectively evaluated in 317 UC patients. The size of the treatment groups was comparable (101 patients UST, 106 anti-TNFα -ADA 24.5%, IFX 65.1%, Golimumab 10.4% and 110 VDZ). At week 16, the efficacy of UST was comparable to that of anti-TNFα and VDZ in terms of clinical response (UST 36.7%, anti-TNFα 46.8%, VDZ 45.9%; p = 0.292), clinical remission (UST 25.6%, anti-TNF 22.3%, VDZ 32.4%; p = 0.475) and steroid-free remission (UST 25.6%, anti-TNFα 22.3%, VDZ 30.3%, p = 0.401) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p70
|
PMC11277193
|
sec[2]/sec[4]/p[5]
|
3.5. Ustekinumab versus Other Therapies in UC
| 4.167969 |
biomedical
|
Study
|
[
0.9970703125,
0.0027980804443359375,
0.0002624988555908203
] |
[
0.998046875,
0.0013103485107421875,
0.0005435943603515625,
0.00022780895233154297
] |
UST was retrospectively compared to the Jak-inhibitor tofacitinib in 289 anti-TNFα–exposed adult patients. Endoscopic remission at week 16 was achieved in 17.0% and 11.7% of patients ( p = 0.47) and histological remission (CFREM +MES ≤ 1 + Nancy index ≤ 1) in 4.4% versus 7.8% in UST- or TOF-treated patients, respectively ( p = 0.32) . However, the authors suggested that compared to TOF, the efficacy of UST could be more impacted by prior therapeutic failures .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277193_p71
|
PMC11277193
|
sec[2]/sec[4]/p[6]
|
3.5. Ustekinumab versus Other Therapies in UC
| 4.152344 |
biomedical
|
Study
|
[
0.974609375,
0.024505615234375,
0.0007114410400390625
] |
[
0.9833984375,
0.01425933837890625,
0.0011339187622070312,
0.0012798309326171875
] |
Similar results were reported in 81 UC patients (45 TOF and 34 UST) following anti-TNFα and anti-integrin failure. Steroid-free clinical remission was similar at week 12/16 (43.9% TOF vs. 40.0% UST; p = 0.82). Drug discontinuation rates or colectomy occurred in 51.1% of patients in the TOF group and 36.1% of patients in the UST group. The occurrence of adverse events was not significantly different (11.1% TOF vs. 5.6% UST, p = 0.57) .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277193_p72
|
PMC11277193
|
sec[2]/sec[4]/p[7]
|
3.5. Ustekinumab versus Other Therapies in UC
| 3.744141 |
biomedical
|
Review
|
[
0.9990234375,
0.00048470497131347656,
0.0005588531494140625
] |
[
0.4423828125,
0.01288604736328125,
0.5439453125,
0.0005249977111816406
] |
Overall, these studies suggest similar efficacy of UST and TOF in UC after anti-TNFα failure. However, considering the faster onset of efficacy of TOF compared to UST, studies comparing the two drugs after longer follow-up are required before drawing definitive conclusions.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p73
|
PMC11277193
|
sec[2]/sec[4]/p[8]
|
3.5. Ustekinumab versus Other Therapies in UC
| 3.644531 |
biomedical
|
Study
|
[
0.99755859375,
0.002044677734375,
0.0006299018859863281
] |
[
0.9384765625,
0.044158935546875,
0.01690673828125,
0.000659942626953125
] |
In the absence of head-to-head data, a placebo-anchored, matching-adjusted, indirect comparison of the induction treatment with UPA versus UST favored UPA, with similar safety profiles, in patients with moderate-to-severe UC. Again, these data need to be confirmed .
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277193_p74
|
PMC11277193
|
sec[2]/sec[5]/p[0]
|
3.6. Dose Escalation and Reinduction in UC
| 3.242188 |
biomedical
|
Review
|
[
0.99755859375,
0.0012340545654296875,
0.0011434555053710938
] |
[
0.302001953125,
0.1317138671875,
0.564453125,
0.0018301010131835938
] |
UST was approved for the treatment of UC in 2019 in the United States and, more recently, in Europe. Thus, less data are available on dose escalation and reinduction of UST, compared to CD, mainly deriving from mixed IBD cohorts, or abstracts of Congress communications in the absence of papers in extenso. Both dose escalation and reinduction, however, improve the efficacy of UST, compared to the standard dose interval.
|
[
"Filippo Vernia",
"Sabrina Monaco",
"Giovanni Latella"
] |
https://doi.org/10.3390/jcm13143993
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.