Higher Weight Based Doses of Adalimumab Reduces Risk of Surgery at 6 Months

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Purpose: Anti-TNFα therapy has demonstrated efficacy in the treatment of moderate-severe Crohn's disease (CD). Both infliximab (IFX) and adalimumab (ADA) have similar rates of remission and response, however both their mode of administration and dosing strategy are different. Whereas IFX is prescribed as a weight based regimen of 5mg/kg or 10 mg/kg infusion, ADA is given subcutaneously in fixed dosing fashion, independent of patient's weight. No study has controlled for weight and its possible effect on remission rates or need for surgical intervention after induction with ADA. Hypothesis: Weight is an important factor in inducing remission in Crohn's disease, and induction regimens with a higher mg/kg dose of ADA are more likely to result in decreased need for surgery. Methods: The Consortium on Outcomes of Biologic Therapy in IBD (COBI) is a prospectively compiled database of patients treated for CD between July 2002 and September 2009 with anti-TNF therapy. A retrospective analysis was performed to determine the effect of induction dosing mg/kg on our primary endpoint, the need for surgical intervention at 6 months time. Both Univariate and Multivariate Analysis were performed. Secondary outcomes were remission and response rates as measured by Harvey Bradshaw Index (HBI). Results: There were 78 patients who received ADA therapy for CD. Of those, only 58 had sufficient data regarding weight, HBI, and surgery to be included in analysis. The mean age for initiation of ADA was 34 years (range 12-73, 56% female). The induction dose was calculated as the mg of ADA received over the 4 week induction period. The range of ADA dosing was 1.73-7.8 mg/kg. There was an association between lower ADA concentration during induction and need for surgical intervention at 6 months (OR 0.49, 95% CI: 0.28-0.84). This held significance in both univariate and multivariate analysis (p=0.009). Initial HBI scores were correlated with need surgical intervention but the study was not powered to detect impact of weight based dosing on remission rates. Conclusion: ADA at higher mg/kg dosing during the induction period of 4 weeks was correlated with a decreased need for surgical intervention at 6 months. The optimal dosing regimen for ADA has been previously described at 160 mg/80 mg, however heavier patients may warrant even higher induction dosing given a likely lower serum concentration in these heavier patients. Trough levels are not commercially available, and existing data has not been stratified by weight. This study demonstrates that a weight based regimen may lead to optimization of ADA. A prospective study where mg/kg dosing is correlated with serum concentration is warranted. Disclosure: Dr Scherl - Speaker's Bureau: Abbott.