Long-term safety and effectiveness of adalimumab in 462 patients with intestinal Behçet’s disease: results from a large real-world observational study

Abstract

Background/aims: The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet's disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet's disease.

Methods: This prospective, all-case, post-marketing study was conducted at 254 centers in Japanese patients with intestinal Behçet's disease receiving adalimumab. The primary endpoint was incidence of adverse drug reactions. Effectiveness endpoints included global improvement rating and change in C-reactive protein levels.

Results: Of the 473 registered patients, 462 and 383 included in the safety and effectiveness populations were administered adalimumab for a mean of 515.3 and 579.5 days, respectively. Overall, 395 patients (85.5%) received adalimumab at the recommended dose. Adverse drug reactions and serious adverse drug reactions were reported in 120 (25.97%) and 51 (11.04%) patients, respectively. The incidence of adverse drug reactions was significantly higher in patients with comorbidities (P< 0.0001), patients taking concomitant oral corticosteroids (P< 0.0001), and those not self-administering adalimumab (P= 0.0257). At study end, global improvement rating was "effective" (n = 156, 40.7%) or "markedly effective" (n = 168, 43.9%) in 324 patients (overall effective, 84.6%). Mean C-reactive protein levels (mg/dL) decreased from 1.96 at baseline (n = 324) to 0.58 at week 24 (n = 208) and 0.25 at week 156 (n = 37).

Conclusions: This large real-world study confirmed the long-term safety and effectiveness of adalimumab in patients with intestinal Behçet's disease. No new safety concerns were identified. (Clinical trial registration number: NCT01960790).

Keywords: Adalimumab; Behçet syndrome; Tumor necrosis factor-alpha.

Conflict of interest statement

Conflict of Interest

Suzuki Y reports grants and personal fees from AbbVie GK, and personal fees from Eisai Co. Ltd., during the conduct of the study; and grants and personal fees from AbbVie GK, EA Pharma Co. Ltd., JIMRO Co. Ltd, KISSEI Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Nippon Kayaku Co. Ltd; personal fees from Eisai Co. Ltd., Gilead Sciences, Inc., Janssen Pharmaceutical K.K., KYORIN Pharmaceutical Co. Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Company, and Zeria Pharmaceutical Co. Ltd., outside the submitted work. Hagiwara T is an employee of AbbVie GK and reports stock/stock options of AbbVie GK outside the submitted work. Kobayashi M, Morita K, and Shimamoto T are employees of AbbVie GK. Hibi T reports grants and personal fees from AbbVie GK, and personal fees from EA Pharma Co. Ltd., during the conduct of the study and outside the submitted work.

Hibi T is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Figures

Fig. 1.

Patient disposition. aSafety information was missing in the case report form (CRF); bGlobal improvement rating data not available.

Fig. 2.

Treatment persistence rate (safety population). aOnly patients with an observation period of 156 weeks were included in this analysis.

Fig. 3.

Incidence of adverse drug reactions (ADRs) by patient background factors (safety population). P-values determined using Fisher exact test. aNot related to Behçet’s disease.

Fig. 4.

Percentage of patients achieving improvement in global gastrointestinal symptom score. P-value determined using Wilcoxon signed-rank test.

Fig. 5.

Improvement in endoscopic findings.

Fig. 6.

Mean change in serum C-reactive protein (CRP) levels. SD, standard deviation.