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Recommended Articles - CD

Ustekinumab For Perianal Crohn’s Disease: The Biolap Multicenter Study From The GETAID

Constance Chapuis-Biron, MD, Julien Kirchgesner, MD, Benjamin Pariente, MD, PhD, Yoram Bouhnik, MD, PhD, Aure´ lien Amiot, MD, PhD, Ste´phanie Viennot, MD, Me´ lanie Serrero, MD, Mathurin Fumery, MD, PhD, Matthieu Allez, MD, PhD, Laurent Siproudhis, MD, PhD, Anthony Buisson, MD, PhD, Guillaume Pineton de Chambrun, MD, PhD, Vered Abitbol, MD, Ste´ phane Nancey,MD, PhD, Ludovic Caillo,MD, Laurianne Plastaras,MD, Guillaume Savoye,MD, PhD, Elise Chanteloup,MD, Marion Simon, MD, Nina Dib, MD, Sylvie Rajca, MD21, Morgane Amil, MD, Anne-Laure Parmentier, Laurent Peyrin-Biroulet, MD, PhD and Lucine Vuitton, MD, PhD1 the GETAID BioLAP Study Group

Am J Gastroenterol 2020;00:1–9.


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Key Take Away Messages

  • The GETAID BioLAP Study Group aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort.
  • This study is the largest real-life multicenter cohort study on patients with pCD treated with Ustekinumab
  • Two hundred seven patients were included.
  • Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab.
  • In 57/148 (38.5%) patients with active pCD at initiation of treatment reached success on perianal disease at 6 months with clinical success and no need for new medical or surgical intervention for perianal lesions.
  • Among patients with setons at initiation, 29/88 (33%) had a successful removal.
  • Among patients with refractory CD and history of but inactive pCD at ustekinumab initiation, the probability of recurrence free survival was 86.2% and 75.1% at weeks 26 and 52, respectively.
  • The authors conclude that ustekinumab appears as a potential effective therapeutic option in perianal refractory CD.
    Further prospective studies are warranted.

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The Effectiveness Of Either Ustekinumab Or Vedolizumab In 239 Patients With Crohn's Disease Refractory To Anti-tumour Necrosis Factor

Hadrien Alric | Aurélien Amiot | Julien Kirchgesner | Xavier Tréton | Matthieu Allez | Yoram Bouhnik | Laurent Beaugerie | Franck Carbonnel | Antoine Meyer

Aliment Pharmacol Ther. 2020;00:1–10.


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Key Take Away Messages

  • The present study aimed to assess effectiveness and safety of vedolizumab and ustekinumab in patients with CD refractory or intolerant to anti-TNF.
  • This analysis is based on a retrospective cohort of patients who initiated either vedolizumab or ustekinumab between May 2014 and August 2018.
  • Hadrien et al. calculated a propensity score with inverse probability of treatment weighting (IPTW), to compare the two treatment groups.
  • Hadrien et al. found that after 1 year of follow-up, ustekinumab was associated with a higher clinical remission rate, greater treatment persistence and less need for optimisation, as compared to vedolizumab.
  • Subgroup analyses showed that patients with ileal and penetrating disease benefited the most from ustekinumab.
  • Regardless of treatment group, combination therapy at initiation with an immunomodulator was associated with a higher rate of clinical remission at W48.
  • Hadrien et al. conclude, this study shows that ustekinumab is associated with higher rates of treatment persistence and clinical remission in patients with anti-TNF refractory CD, particularly in those with ileal and penetrating disease. There was no significant difference in steroid-free clinical remission between patients treated with ustekinumab and vedolizumab.

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IM-UNITI: Three-year Efficacy, Safety, And Immunogenicity Of Ustekinumab Treatment Of Crohn’s Disease

Stephen B. Hanauer, William J. Sandborn, Brian G. Feagan, Christopher Gasink, Douglas Jacobstein, Bin Zou, Jewel Johanns, Omoniyi J. Adedokun, Bruce E. Sands, Paul Rutgeerts

Journal of Crohn's and Colitis, 2020, 23–32


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Key Take Away Messages

  • IM-UNITI is a 5-year maintenance study designed to evaluate the efficacy and safety of long-term ustekinumab therapy for CD.
  • In this article Stephen et al. report that in ustekinumab induction responders, remission and response rates were generally maintained in both TNF antagonist failure and non-failure populations through Week 152.
  • Rates of maintenance of remission were more stable among the TNF antagonist non-failure population and in patients who had not experienced dose adjustment preceding Week 44.
  • Both q8w and q12w week ustekinumab SC dosing regimens were effective, and the difference between the dosing regimens was not clinically meaningful from Week 92 to Week 152.
  • All patients remained on stable dosing without dose adjustment in the LTE. It is notable that 43% of the q8w and 38% of the q12w SC ustekinumab groups are in remission at Week 152, using this most stringent analysis.
  • Rates of antibodies to ustekinumab in the randomized CD Phase 3 programme were low; 2.3% through Week 44, 4.2% at Week 96, and 4.6% through Week 156, and were low either with or without the use of concomitant immunomodulators. Antibody positivity was not related to efficacy.
  • The overall rates of adverse events and serious adverse events were comparable to placebo through Week 156. No new safety signals were identified between Weeks 96 and 156.
Summary of the efficacy results for the IM-UNITI study through Week 152 and safety results through Week 156, presented by Stephen et al, provide additional data on the long-term treatment effects of ustekinumab, highlighting the sustainability of the clinical effects of ustekinumab through 3 years with continued low rates of immunogenicity.

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Systematic Review And Network Meta-analysis: First- And Second-line Biologic Therapies For Moderate-severe Crohn's Disease

S. Singh | M. Fumery | W. J. Sandborn | M. H. Murad

Aliment Pharmacol Ther. 2018;48:394-409


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Key Take Away Messages

  • Singh et al. conducted a systematic review with pairwise and network meta-analyses, comparing the relative efficacy and safety of anti-TNF agents (infliximab, adalimumab, certolizumab pegol), anti-integrin agents (vedolizumab) and anti-IL12/23 agents (ustekinumab), as first- and second-line agents in patients with moderate-severe CD.

The authors conclude

  • In biologic-naıve patients, anti-TNF agents, infliximab and adalimumab, are ranked highest for inducing clinical remission and response.
  • In patients with prior exposure to anti-TNF agents, moderate quality evidence supports the use of ustekinumab, and low-quality evidence supports the use of vedolizumab as second-line agent, for induction of clinical remission.
  • In maintenance trials, no specific agent was clearly safer than others.

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Pharmacokinetics And Exposure Response Relationships Of Ustekinumab In Patients With Crohn’s Disease

Omoniyi J. Adedokun, Zhenhua Xu, Christopher Gasink, Douglas Jacobstein, Philippe Szapary, Jewel Johanns, Long-Long Gao, Hugh M. Davis, Stephen B. Hanauer, Brian G. Feagan, Subrata Ghosh, and William J. Sandborn

Gastroenterology 2018;154:1660–1671


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Key Take Away Messages

  • Adedokun at al. collected data from 2 Phase 3 induction studies and 1 maintenance study to determine ustekinumab’s pharmacokinetic features, relationship between exposure and response, and optimal serum concentrations for efficacy.
  • Strong positive associations were seen between ustekinumab concentration and clinical efficacy outcomes in induction.
  • Strong positive correlations were seen between steady-state trough ustekinumab concentrations and remission with both maintenance regimens (90 mg SC q12w and q8w).
  • Based on the ROC analyses, steady-state concentration cutoffs ranging between 0.8 and 1.4 mg/mL were associated with greater clinical remission during maintenance, corroborating the quartile analysis.
  • The incidence of antibodies to ustekinumab through 1 year on treatment was 2.3% (using a drug-tolerant assay), indicating that ustekinumab has low immunogenicity.
  • In contrast to the experience with TNF antagonists, there was no significant impact of AZA, 6-MP, or MTX on serum ustekinumab concentration and immunogenicity.

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Efficacy Of Ustekinumab For Inducing Endoscopic Healing In Patients With Crohn’s Disease

Paul Rutgeerts, Christopher Gasink, Daphne Chan, Yinghua Lang, Paul Pollack, Jean-Frederic Colombel, Douglas C. Wolf, Douglas Jacobstein, Jewel Johanns, Philippe Szapary, Omoniyi J. Adedokun, Brian G. Feagan and William J. Sandborn

Gastroenterology 2018;155:1045–1058


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Key Take Away Messages

  • In this prospective substudy within the UNITI-1 and -2 induction and IM-UNITI maintenance studies, Rutgeerts at al. evaluated the efficacy of ustekinumab for the induction and maintenance of endoscopic healing in patients with moderately to severely active CD.
  • Patients given IV ustekinumab had greater endoscopic improvement at week 8 than placebo.
  • Endoscopic improvement was better maintained at week 44 in patients given SC ustekinumab maintenance therapy than placebo.
  • Ustekinumab demonstrated the ability to reduce endoscopic inflammation and was effective for inducing endoscopic healing.

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Long-term Efficacy And Safety Of Ustekinumab For Crohn’s Disease Through The Second Year Of Therapy

W. J. Sandborn | P. Rutgeerts | C. Gasink | D. Jacobstein | B. Zou | J. Johanns | B. E. Sands | S. B. Hanauer | S. Targan | S. Ghosh | W. J. S. de Villiers | J.-F. Colombel | B. G. Feagan

Aliment Pharmacol Ther. 2018;1–13.


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Key Take Away Messages

  • IM-UNITI is the 5-year maintenance study in the Phase 3 pivotal programme for treatment of patients with Crohn’s disease with ustekinumab.
  • In this article Sandborn at al. report the IM-UNITI long-term extension data demonstrating the maintenance of response and remission (Week 92) with a positive safety profile (Week 96).
  • The findings confirm that in ustekinumab induction responders, remission, and response rates were maintained through Week 92 of the study in both TNF antagonist-refractory patients from UNITI-1 and UNITI-2 conventional therapy failure patients (predominantly TNF antagonist-naive).
  • Efficacy from Week 44 to Week 92 of subcutaneous ustekinumab maintenance in patients entering the long-term extension was similar for both the every 8 weeks and every 12 weeks subcutaneous ustekinumab dose regimens, in both populations.
  • Clinical results were supported by maintained normalization of CRP concentrations and improved health-related quality of life outcome measures.
  • Rates of patients who developed anti-drug antibodies were low and formation of antibodies did not impact response and remission rates.
  • Ustekinumab was well tolerated with a favorable safety profile that did not differentiate from placebo.
  • No new safety signals were observed.

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Ustekinumab As Induction And Maintenance Therapy For Crohn’s Disease

B.G. Feagan, W.J. Sandborn, C. Gasink, D. Jacobstein, Y. Lang, J.R. Friedman, M.A. Blank, J. Johanns, L.-L. Gao, Y. Miao, O.J. Adedokun, B.E. Sands, S.B. Hanauer, S. Vermeire, S. Targan, S. Ghosh, W.J. de Villiers, J.-F. Colombel, Z. Tulassay, U. Seidler, B.A. Salzberg, P. Desreumaux, S.D. Lee, E.V. Loftus, Jr., L.A. Dieleman, S. Katz, and P. Rutgeerts, for the UNITI–IM-UNITI Study Group

N Engl J Med 2016;375:1946-60


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Key Take Away Messages

• This article summarizes the results of three phase 3 studies for the treatment of Crohn’s disease with ustekinumab.

Two 8-week induction trials:
The UNITI-1 trial - anti TNF Failure population
The UNITI-2 trial - anti TNF naïve population

One 44-week maintenance trial:
The IM-UNITI trial patients who had a response to ustekinumab induction in induction trials.
Rapid efficacy

Rapid Efficacy
  • In both induction trials, the primary end point to achieve a clinical response at week 6, which was defined as a decrease from baseline in CDAI score of at least 100 points or a total CDAI score less than 150 was reached.
  • The benefits of ustekinumab in inducing a response were observed as early as week 3. This prompt onset of clinical efficacy, paralleled by decreases in CRP levels, is desirable in such highly symptomatic patients.
Maintenance Results
  • In IM-UNITI, superiority over placebo was shown for both the primary outcome and the majority of the secondary end points.
  • In both of the groups receiving maintenance doses of subcutaneous ustekinumab, patients had significantly lower CRP and fecal calprotectin levels at week 44 than those who received placebo.
  • CONCLUSIONS:Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy

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למידע מלא על התכשיר (כולל תופעות לוואי) יש לעיין בעלון לרופא המאושר ע"י משרד הבריאות

EM-52720


Published

June 3, 2021