Short- and long-term efficacy of adalimumab salvage therapy after failure of calcineurin inhibitors in steroid-refractory ulcerative colitis

Abstract

Objective: Calcineurin inhibitors are highly effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with calcineurin inhibitors fails, adalimumab can be considered to avoid colectomy. The efficacy and safety of this sequential alternative salvage therapy remain unknown. Therefore, the present study was performed to investigate the short- and long-term efficacy and safety of adalimumab after failure of calcineurin inhibitors in corticosteroid-refractory UC.

Materials and methods: Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan–Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. The cumulative rates of colectomy were calculated. Predictive factors for clinical remission and colectomy were identified. In the safety evaluation, any adverse event occurring after the administration of adalimumab was considered.

Results: Forty-one patients were enrolled; 78% had extensive colitis and 87% had moderate to severe colitis. Seventeen patients (41%) underwent colectomy during the follow-up period. At week 8, 26, and 52 after adalimumab injection, 27%, 39%, and 32% of patients achieved clinical remission, respectively. The adverse event rate was 17%, including one case of tuberculosis.

Conclusions: The efficacy of adalimumab for calcineurin inhibitor-refractory UC was examined for the first time. Treatment with adalimumab avoided the need for colectomy in two-thirds of patients with corticosteroid-refractory UC in whom calcineurin inhibitors had failed. However, attention is needed to avoid adverse events, especially infection.

Keywords:

• Ulcerative colitis
• adalimumab
• anti-tumour necrosis factor monoclonal antibodies
• calcineurin inhibitor
• remission
• colectomy
• salvage
• tacrolimus
• cyclosporine

Acknowledgments

We thank Angela Morben, DVM, ELS, and Clare Cox, PhD, from Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.

Disclosure statement

RK received personal fees and grants, scholarships, and funded research/collaborative research from Abbott Japan Co., Ltd.; AbbVie GK; AJINOMOTO Co., Inc.; Asahi Kasei Medical Co., Ltd.; Astrazeneca Co., Ltd.; Astellas Pharm Inc.; EA Pharma Co., Ltd.; Eisai Co., Ltd.; Janssen Pharmaceutical K.K.; JIMRO Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Kyorin Pharmaceutical Co., Ltd.; Kyowa Hakko Kirin Co., Ltd.; Otsuka Pharmaceutical Co., Ltd.; Nippon Kayaku Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; Takeda Pharma Co., Ltd.; and Zeria Pharmaceutical Co., Ltd. HK received personal fees and grants, scholarships, and funded research/collaborative research from AbbVie GK; Astellas Pharma Inc.; EA Pharma Co., Ltd.; Janssen Pharmaceutical K.K.; JIMRO Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Kyorin Pharmaceutical Co., Ltd.; Kyowa Hakko Kirin Co., Ltd.; Medical View Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; Mochida Pharmaceutical Co., Ltd.; Shire Japan K.K.; and Zeria Pharmaceutical Co., Ltd. SM received personal fees and grants, scholarships, and funded research/collaborative research from Grant-in-Aid for Scientific Research; Merck Serono Co., Ltd.; Zeria Pharmaceutical Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Pfizer Inc.; Bristol-Myers Squibb K.K.; Astellas Pharma Inc.; Daiichi-Sankyo Co., Ltd.; Takeda Pharma Co., Ltd.; MSD K.K.; and Gilead Sciences. The other authors have no conflicts of interest.