Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial

Sands, Bruce E.; Hoops, Timothy; Izanec, James; Gao, Lei; Gasink, Christopher; Greenspan, Andrew; Hanauer, Stephen B.; Kuehbacher, Tanja; Lewis, James D.; Scherl, Ellen; Sandborn, William J.; Afzali, Anita; Aitova, Lilia; Mante, Xavier Aldeguer i; Allez, Matthieu; Altorjay, István; Arias, Federico Argüelles; Armuzzi, Alessandro; Augustyn, Monika; Boiocchi, Mauro; Barrio, Jesús; Begun, Jakob; Behrend, Clint; Bezemer, Geert; Bonnaud, Guillaume; Branković, Marija; Byung, Ik Jang; Calvo, Xavier Calvet; Chachu, Karen A.; Chebli, Júlio Maria Fonseca; Cheon, Jae Hee; Cichoż‐Lach, Halina; Clark, Larry; Cummings, Fraser; Dalal, Kunal; Danese, Silvio; Boer, Nanne de; Ferrari, Maria de Lourdes Abreu; Désilets, Étienne; Dugalić, Predrag; Duvall, George; Fedorishina, Olga; Filip, Rafał; Flores, Cristina; Fogel, Ronald; Fon, James; Frankel, Michael; Friedenberg, Keith; Fries, Walter; Galina, Vassileva; Gietka, Piotr; Goel, Rishi; Hasselblatt, Peter; Herfarth, Hans H; Herszényi, László; Hindryckx, Pieter; Hoentjen, Frank; Horje, Carmen Horjus Talabur; Iduru, Satish; Irving, Peter M.; Isfort, Robert J.; Jairath, Vipul; Jones, Michael P.; Kalimullina, Dilara; Katz, Jeffry; Kaur, Manreet; Khurana, Sunil K; Kim, Sang Woo; Kim, Young‐Ho; Kleczkowski, D; Knežević, S; Knoll, Aaron; Korman, Louis Y; Kotzev, Iskren; Kulyapin, Andrey; Lee, Kang Moon; Leemreis, Desirée; Leszczyszyn, Jarosław; Limdi, Jimmy K.; Lissauer, Jack J.; Loftus, Edward V.; Małecka‐Panas, Ewa; Marshall, John K.; Mihály, Emese; Lukáš, Milan; Monteleone, Giovanni; Nagorni, Aleksandar; Owczarek, Danuta; Palekar, Nichole; Panaccione, Remo; Park, Young Soo; Park, Sang Hyoung; Parra, Rogério Serafim; Patai, Árpád V.; Patel, Kamal; Patel, Bhaktasharan; Pershko, Anatoly; Petrova, Elina; Chambrun, Guillaume Pineton de; Randall, Charles; Menéndez, S. Riestra; Ritter, Timothy E.; Rivero, Montserrat; Roblin, Xavier; Rocca, Rodolfo; Romatowski, J; Rydzewska, Grażyna; Saibeni, Simone; Salzberg, Bruce; Sarles, H; Saunders, John B.; Savarino, Edoardo; Šerclová, Zuzana; Щукина, О. Б.; Siegel, Jonathan H.; Soofi, Najm; Sparrow, Miles P.; Stokesberry, David; Suiter, Daniel; Svorcan, Petar; Tkachev, Alexander; Tsonev, Nikolay; Kristóf, Tünde; Ulbrych, Jan; Vaňásek, Tomáš; Varga, Márta; Vermeire, Séverine; Lidon, Raquel Vicente; Weiss, Michael L; Wesley, Emma; Winstead, Nathaniel S.; Wójcik, Katarzyna; Wypych, Joanna; Zaltman, Cyrla; Zadorova, Zdena

doi:10.1016/s0140-6736(22)00688-2

Cited by 157 publications

(97 citation statements)

References 32 publications

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“…Agreement between investigators for study eligibility was excellent (kappa statistic=0.85). Eighteen articles reported on 19 induction of remission RCTs only9 16 17 34–47 (NCT00291668); five articles reported six induction of remission trials together with rerandomisation of patients in these RCTs into five subsequent maintenance of remission trials48–52; and 10 articles reported maintenance of remission RCTs only 10 53–61. In total, therefore, there were 23 articles reporting on 25 separate induction of remission RCTs9 16 17 34–52 (NCT00291668) and 15 articles reporting on 15 separate maintenance of remission trials 10 48–61.…”

Section: Resultsmentioning

confidence: 99%

“…Characteristics of individual studies are provided in online supplemental table 3, and risk of bias of all trials is provided in online supplemental table 4. Fifteen induction of remission RCTs, reported in 14 articles,34–36 38–40 42 43 45 47–50 52 were low risk of bias across all domains. The 15 maintenance of remission trials included 4016 patients, randomised to active drug or placebo (online supplemental table 5), one of which was reported online 61.…”

Section: Resultsmentioning

confidence: 99%

“…All 25 induction of remission trials reported data for this endpoint at between 4 weeks and 16 weeks9 16 17 34–52 (NCT00291668). The network plot is provided in figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Clinical response was reported by 24 induction of remission trials at 6–12 weeks (online supplemental figure 6)9 16 17 34–45 47–52 (NCT00291668). There was low heterogeneity between studies (τ 2 =0.0109), and the funnel plot appeared symmetrical (online supplemental figure 7).…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis

Barberio

Gracie

Black

et al. 2022

Gut

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ObjectiveThere are numerous biological therapies and small molecules licensed for luminal Crohn’s disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis.DesignWe searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score.ResultsWe identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82).ConclusionIn a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…All 25 induction of remission trials reported data for this endpoint at between 4 weeks and 16 weeks9 16 17 34–52 (NCT00291668). The network plot is provided in figure 1.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis

Barberio

Gracie

Black

et al. 2022

Gut

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“…According to the seventh national census data, the national population is 1,411.78 million, and the population aged 60 and above is 264.02 million, accounting for 18.70% (among them, the population aged 65 and above is 190.64 million, accounting for 13.50%). Compared with 2010, the proportion of the population aged 60 and above has increased by 5.44 percentage points [ 1 ]. The level of rural economic development is backward, the self-security ability of farmers is poor, and they do not have the economic ability and willingness to purchase professional pension services.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Interpersonal Trust on Rural Residents’ Willingness to Participate in Mutual Aid for the Aged: An Empirical Analysis Based on the Survey Data of Hubei and Henan Provinces

Liu

Yong-yong

2022

Computational Intelligence and Neuroscience

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At present, there is a huge gap between supply and demand of old-age services in rural areas of China. Developing rural mutual old-age services is of great significance to remedy the gap. Based on the survey data of 1200 rural residents in Hubei and Henan provinces, this paper adopts binary logistic regression model to analyze the influence of special trust and general trust on rural residents’ willingness to participate in mutual care for the aged. The results show that both special trust and general trust have an impact on rural residents’ willingness to participate in mutual support for the elderly, but the effect of special trust on rural residents’ willingness to participate in mutual support for the elderly is not significant. General trust has a significant promoting effect on rural residents’ willingness to participate in mutual care for the aged. Chinese rural residents’ trust in village cadres has a significant promoting effect on their willingness to participate in mutual assistance for the aged. The trust of ordinary friends significantly inhibited their willingness to participate. The educational level, living style, and economic status of Chinese rural residents have a positive impact on their willingness to participate in mutual care for the aged. Age, marital status, health status, and intergenerational relationship are inversely correlated with willingness to participate.

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Model‐Informed Assessment of Probability of Phase 3 Success for Ritlecitinib in Patients with Moderate‐to‐Severe Ulcerative Colitis

Wojciechowski,

Mukherjee,

Banfield

et al. 2024

Clin Pharma and Therapeutics

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Ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family inhibitor, was evaluated in patients with ulcerative colitis (UC) in a phase 2b trial. Model‐informed drug development strategies were applied to bridge observations from phase 2b to predictions for a proposed phase 3 study design to assess the probability of achieving the target efficacy outcome. A longitudinal exposure‐response model of the time course of the 4 Mayo subscores (rectal bleeding, stool frequency, physician's global assessment, and endoscopic subscore) in patients with UC receiving placebo or ritlecitinib was developed using population modeling approaches and an item response theory framework. The quantitative relationships between the 4 Mayo subscores accommodated the prediction of composite endpoints such as total Mayo score and partial Mayo score (key endpoints from phase 2b), and modified clinical remission and endoscopic remission (proposed phase 3 endpoints). Clinical trial simulations using the final model assessed the probability of candidate ritlecitinib dosing regimens (including those tested in phase 2b and alternative) and phase 3 study designs for achieving target efficacy outcomes benchmarked against an approved treatment for moderate‐to‐severe UC. The probabilities of achieving target modified clinical remission and endoscopic improvement outcomes at both weeks 8 and 52 for ritlecitinib 100 mg once daily was 74.8%. Model‐based assessment mitigated some of the risk associated with proceeding to pivotal phase 3 trials with dosing regimens of which there was limited clinical experience.

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Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial

Cited by 157 publications

References 32 publications

Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis

Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis

The Influence of Interpersonal Trust on Rural Residents’ Willingness to Participate in Mutual Aid for the Aged: An Empirical Analysis Based on the Survey Data of Hubei and Henan Provinces

Model‐Informed Assessment of Probability of Phase 3 Success for Ritlecitinib in Patients with Moderate‐to‐Severe Ulcerative Colitis

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