Safety of Adalimumab and Predictors of Adverse Events in 1693 Japanese Patients with Crohn's Disease

Abstract

Background and aims: Data from an all-cases post-marketing study were used to evaluate the safety and effectiveness of adalimumab in Japanese patients with Crohn's disease [CD].

Methods: Patients received adalimumab for 24 weeks. Data from all patients [n = 1693] were used for the safety assessment. Data from patients with CD activity index [CDAI] ≥ 150 at baseline were used for the effectiveness assessment.

Results: The most frequent serious adverse drug reaction [ADR] was infection and infestations [6.6 events/100 patient-years]. The risk of serious infections increased in patients who had a history of malignancy and those with concomitant corticosteroid use. Of 415 patients who had switched from another anti-tumour necrosis factor alpha [TNFα] agent to adalimumab due to ADRs, 7.2% discontinued due to ADRs to adalimumab. Ten of 13 patients with a history of tuberculosis [TB] received prophylactic medication, and none developed TB. TB developed in one patient with no history of TB or anti-TB prophylaxis. Remission rates were 41.3% and 32.4% at 4 and 24 weeks, respectively. Remission rates did not differ between patients with and without concomitant use of immunomodulators. Predictive variables for increased effectiveness were CDAI ≤ 220 and disease duration of ≤ 2 years. Perianal lesions and loss of response to previous anti-TNFα agents affected effectiveness.

Conclusions: The most frequent serious ADR was infection. Adalimumab significantly reduced disease activity, without any unexpected ADRs. Development of active TB during adalimumab therapy can be prevented through TB screening and prophylaxis. In patients who switched from another anti-TNFα agent to adalimumab due to ADRs, adalimumab was well tolerated.

Keywords: Adalimumab; Crohn’s disease; post-marketing study.

© European Crohn’s and Colitis Organisation 2016.

Figures

Figure 1.

Patient disposition. CDAI, Crohn’s disease activity index.

Figure 2.

Factors affecting the safety of adalimumab identified by multiple logistic regression analysis for a] serious adverse drug reactions [ADRs] and b] serious infections. ap-value was calculated using Wald’s chi-square test. CI, confidence interval; OR, odds ratio.

Figure 2.

Factors affecting the safety of adalimumab identified by multiple logistic regression analysis for a] serious adverse drug reactions [ADRs] and b] serious infections. ap-value was calculated using Wald’s chi-square test. CI, confidence interval; OR, odds ratio.

Figure 3.

Patients achieving remission at 4 weeks and 24 weeks by non-responder imputation [NRI] and as-observed analyses.

Figure 4.

Factors affecting the effectiveness of adalimumab identified by multiple logistic regression with as-observed analysis [patients were considered responders if they showed a response at 24 weeks]. ap-value was calculated using Wald’s chi-square test. CI, confidence interval; CDAI, Crohn’s Disease Activity Index; OR, odds ratio; TNFα, tumour necrosis factor alpha.