The efficacy of rebamipide add-on therapy in arthritic patients with COX-2 selective inhibitor-related gastrointestinal events: a prospective, randomized, open-label blinded-endpoint pilot study by the GLORIA study group

Abstract

Objective We aimed to confirm the effect of combined treatment with celecoxib and rebamipide would be more effective than celecoxib alone for prevention of upper gastrointestinal (GI) events.

Methods Patients with rheumatoid arthritis, osteoarthritis, and low back pain were enrolled in this study. Patients were randomized to two groups: a monotherapy group (100 mg celecoxib twice daily) and a combination therapy group (add on100 mg of rebamipide three times a day). The GI mucosal injury was evaluated by endoscopic examination before treatment and at 3 months. The primary endpoint was to evaluate the preventive effect of the combination therapy group for GI events, endoscopic upper GI ulcers and intolerable GI symptoms, compared with the monotherapy group.

Results Seventy-five patients were enrolled. Sixty-five patients were analyzed (16 males, 49 females; mean age: 67 ± 13 years). The prevalence of upper GI events, five of endoscopic GI ulcers and one of intolerable GI symptoms, were 6/34 (17.6 %) in the monotherapy group and 0/31 in the combination therapy group, p = 0.0252.

Conclusions The combination therapy group was more effective than the monotherapy group for prevention of upper GI events in this study. Rebamipide might be a candidate for an option to prevent COX-2 selective inhibitor-induced upper GI events.

Keywords::

• Gastrointestinal tract
• NSAIDs
• COX-2 inhibitors
• Rheumatoid arthritis
• Osteoarthritis

Acknowledgments

We acknowledge the contributions of Takeshi Nagakura, Kunikazu Ogawa, Hiroshi Hasegawa, Hitoshi Inada, Katsumi Mukai, Eiji Kawakita, Kimiaki Nishikubo, Takahiko Hamaguchi, Takahisa Hara, Toshio Yamaguchi, Shuji Obata, Hirohito Suzuki, Ken Nakaseko, Hideki Tsutsumi, Shigeru Omori, Masashi Morimoto, Ryu Iida, Yoshihiro Wakita, Koichiro Morishita, Ken Shintani, and Mitsumasa Kimura of the GLORIA [Preventive Effect on Gastric Mucosal Lesion in Patients with Osteoarthritis or Rheumatism Arthritis by COX-2 Inhibitor and Anti-ulcer Agent (Rebamipide) Combination Therapy] study group; Masakatsu Nishikawa, Satoshi Tamaru, and Tomomi Yamada, who provided statistical support; and Chisato Minamide, Yasuyuki Ohta, Manami Kobata, and Yoko Uhira at the Mie Clinical Trials Support Network Center.

Conflict of interest

None.