Background Patients with rheumatoid arthritis (RA) with moderate to high disease activity are primarily treated with disease-modifying anti-rheumatic drugs (DMARDs). Since the late 1990s, patients who do not achieve remission despite methotrexate (MTX) treatment have been treated with biologic agents (biologics) with the goal of reducing synovial inflammation and preventing joint destruction [1-3]. Although efficacy and safety of biologics have been established in many clinical studies, safety in elderly patients remains unclear.
Objectives To clarify the safety of biologics in elderly patients with RA and to identify factors related with discontinuation.
Methods RA patients who were initiated infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT) as the first biologic agent from January 2012 to December 2014 were enrolled in this retrospective single-center study. We classified patients into three groups according to their age (young, <65 years old (y/o); elderly, 65-74 y/o; old elderly, ≥75 y/o) and compared background characteristics, adverse effects, and drug discontinuation rates.
Results Two hundred sixteen patients (IFX, n=73; TCZ, n=92; ABT, n=51) were enrolled; female, 84.3%, mean age 59±15 years old, mean disease duration 9.3±15 years. The mean observation period was 59.6±43.9 (0-154) weeks. One hundred twenty five patients (57.9%) were classified in the young group, fifty six patients (25.9%) in the elderly group, and thirty five patients (16.2%) in the old elderly group. The background characteristics depicted in the Table. Considerable variations were observed in disease duration, HAQ-DI and the usage of MTX among the 3 groups. IFX and TCZ were frequently used in young group while ABT was the most preferable biologic agent in the old elderly group. During the observation period, 8.8% of young group, 17.9% of elderly group, and 17.1% of old elderly group discontinued biological due to adverse events (infection was 1 in each group). Although the discontinuation rate due to adverse events was the lowest in young group, there was no significant difference among three groups (P=0.15, Figure). When we compared the background characteristics between elderly group and old elderly group, disease duration was longer and HAQ-DI was worse (P 0.04, 0.03, respectively) in old elderly group, Brinkman index (P=0.04) was lower, and the complication with pulmonary diseases and cardiovascular diseases were inclined, although not statistically significant, to be lower in very elderly group than those in elderly group. 2 patients in elderly group unexpectedly died (causes unknown), and both had smoking habit, comorbid pulmonary diseases and cardiovascular diseases.
Conclusions Being cautious with Brinkman index and the presence of complicated diseases, using biologic agents in elderly patients with RA is a safe choice of treatment.
Smolen JS, et al. Ann Rheum Dis. 2014, 73:492-509.
Lipsky PE, et al. N Engl J Med. 2000, 343:1594-1602.
Smolen JS, et al. Ann Rheum Dis. 2012, 71:687-693.
Disclosure of Interest A. Murota: None declared, Y. Kaneko Consultant for: Abbvie, Paid instructor for: Eisai Pharmaceutical, Chugai Pharmaceutical, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Speakers bureau: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Janssen, UCB, K. Yamaoka Consultant for: Pfizer Japan Inc., Speakers bureau: Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd, Eli Lilly Japan K.K.,Astellas Pharma, GlaxoSmithKline K.K., Nippon Shinyaku Co., Ltd. and Actelion Pharmaceuticals Japan Ltd., T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd.,SymBio Pharmaceuticals Ltd., Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co., Ltd., Bristol-Myers K.K., Nipponkayaku Co.Ltd., Paid instructor for: Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., Abbivie GK., Speakers bureau: AbbVie GK., Bristol-Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Diaichi Sankyo Co.,Ltd., Celtrion and Nipponkayaku Co.Ltd.