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Randomized Controlled Trial
. 2019 May;49(9):1188-1194.
doi: 10.1111/apt.15214. Epub 2019 Mar 19.

Early combined immunosuppression may be effective and safe in older patients with Crohn's disease: post hoc analysis of REACT

Siddharth Singh  1   2 , Larry W Stitt  3 , Guangyong Zou  3   4 , Reena Khanna  3   5 , Parambir S Dulai  1 , William J Sandborn  1 , Brian G Feagan  3   4   5 , Vipul Jairath  3   4   5
Affiliations
Randomized Controlled Trial

Early combined immunosuppression may be effective and safe in older patients with Crohn's disease: post hoc analysis of REACT

Siddharth Singh et al. Aliment Pharmacol Ther. 2019 May.

Abstract

Background: Physicians may be reluctant to prescribe combined immunosuppression in older patients with Crohn's disease due to perceived risk of treatment-related complications.

Aim: To evaluate the impact of age on risk of Crohn's disease-related complications in patients treated with early combined immunosuppression vs conventional management in a post hoc analysis of the randomised evaluation of an algorithm for Crohn's treatment (REACT), a cluster-randomised trial.

Methods: We compared efficacy (time to major adverse outcome of Crohn's disease-related surgery, hospitalisation or serious complications; corticosteroid-free clinical remission) and safety outcomes at 24 months, between patients aged <60 vs ≥60 years randomised to early combined immunosuppression or conventional management, using Cox proportional hazard analysis or modified Poisson model. In the early combined immunosuppression arm, patients with failure to achieve clinical remission within 4-12 weeks of corticosteroids were treated with a combination of tumour necrosis factor-α antagonist plus anti-metabolite and sequentially escalated in a stepwise algorithm.

Results: Of 1981 patients, 311 were ≥60 years (15.7%; 173 randomised to early combined immunosuppression and 138 to conventional management). Over 24 months, 10% of older patients developed Crohn's disease-related complications (early combined immunosuppression vs conventional management: 6.4% vs 14.5%) and 14 patients died (3.5% vs 5.8%). There was no difference between younger and older patients in risk of achieving corticosteroid-free clinical remission (<60 years, early combined immunosuppression (72.6%) vs conventional management (64.4%): relative risk [RR], 1.06 [95% CI, 0.98-1.15] vs ≥60 years, early combined immunosuppression (74.8%) vs conventional management (63.0%): RR, 1.09 [0.90-1.33], P-interaction = 0.78) or time to major adverse outcome (<60 years: hazard ratio [HR], 0.71 [0.53-0.96] vs ≥60 years: HR, 0.69 [0.31-1.51], P-interaction = 0.92) with early combined immunosuppression vs conventional management.

Conclusions: We observed no difference in efficacy and safety of early combined immunosuppression compared to conventional management in older and younger patients. Early combined immunosuppression may be considered as a treatment option in selected older patients with Crohn's disease with suboptimal disease control. Clinical Trial Identifier: NCT01030809.

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Conflict of interest statement

Conflicts of Interest

Siddharth Singh: Research support from Pfizer and AbbVie, consulting fees from AbbVie and Takeda, outside the submitted work

Larry Stitt: None

Reena Khanna: Fees for Consulting/Speaking from: AbbVie, Encycle, Janssen, Pendopharm, Pfizer, Robarts Clinical Trials, Shire, and Takeda Canada outside the submitted work

Parambir Dulai: Research support from Pfizer, and has received research support, travel support and served as a consultant for Takeda outside the submitted work

Guangyong Zou: None

William Sandborn: Research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos; consulting fees from Abbvie, Allergan, Amgen, Boehringer Ingelheim, Celgene, Conatus, Cosmo, Escalier Biosciences, Ferring, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Miraca Life Sciences, Nivalis Therapeutics, Novartis Nutrition Science Partners, Oppilan Pharma, Otsuka, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix, Shire, Seres Therapeutics, Sigmoid Biotechnologies, Takeda, Tigenix, Tillotts Pharma, UCB Pharma, Vivelix; and stock options from Ritter Pharmaceuticals, Oppilan Pharma, Escalier Biosciences, Gossamer Bio, Precision IBD, Progenity

Brian Feagan: Received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma; and speakers bureaux fees from UCB, AbbVie, and J&J/Janssen

Vipul Jairath: Consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer

Figures

Figure 1.
Figure 1.
Early Combined Immunosuppression algorithm in REACT
See this image and copyright information in PMC

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