Introduction Adalimumab (ADA) is effective for the induction and maintenance of remission in Crohn’s disease (CD) patients. Although the approved maintenance regimen is 40 mg subcutaneously every 14 days, some patients require dose-escalation (DE).
Methods Aim of the study was to describe a large, well-characterised cohort of ADA treated CD patients in a tertiary referral centre and to identify factors predicting the need for DE. A prospectively maintained database of CD patients treated with ADA at the Guy’s and St Thomas’ IBD Center between 2007–2012 was interrogated. Clinical and phenotypic details and exposure to therapy were analysed. Survival and regression analyses were performed.
Results 112 CD (50% Male) patients commenced ADA. Three patients had coexisting Oro-Facial Granulomatosis. Mean age at diagnosis was 22 (SD; 9) years. Disease location was ileo-colonic (68.8%) in the majority. Upper gastrointestinal (UGI) involvement was found in 17.9%, peri-anal disease in 29.5% and extra-intestinal manifestations in 14.3%.
Median duration of disease prior to ADA initiation was 11 years (IQR; 5–18). Previous infliximab (IFX), ADA and exposure to both were found in 59, 3 and 7 patients respectively. Of the 66 patients exposed to IFX 29 (43.9%) had primary or secondary loss of response. A total of 82 (71.3%) were on concomitant immunomodulators ((CIM) - azathioprine, mercaptopurine, thioguanine or methotrexate) at the time of initiation of ADA.
103 (89.3) patients responded to ADA induction. 4 patients were primary non-responders, 5 withdrew due to adverse effects. All 4 primary non-responders and 3/5 who withdrew were previously exposed to IFX.
DE was required in 40 (38.8%) of the responders during the follow-up period at a median 26 months (95% confidence interval (CI); 19.6- 32.4). Cumulative probability of requiring DE at 24 months was 52% (CI: 42–62). CIM at initiation of ADA (Odds ratio (OR): 0.21, CI: 0.09–0.47, p < 0.0001), previous IFX exposure (OR: 4.27, CI: 1.73–10.55, p = 002) and UGI involvement (OR: 3.43, CI: 1.02–11.42, p = 0.046) were independently associated with need for DE in multivariate analysis. CIM at commencement of ADA was associated with increased time to DE (Hazard ratio: 0.34, CI: 0.18–0.64, p = 0.001). 24/38 (63.25%) patients responded to DE, 2 patients had incomplete follow-up data.
Conclusion 38.8% of CD patients commencing ADA in this well defined cohort required DE due to loss of response, of which 63% were recaptured. CIM at initiation predicted a more durable response to standard dosing. UGI involvement and previous exposure to IFX were associated with increased risk of requiring DE.
Disclosure of Interest None Declared.
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