Background Incidence and prognosis of nontuberculous mycobacterium (NTM) infection in patients with rheumatoid arthritis (RA) is reported to be worse than general population, especially when treated with biological agents such as tumor necrosis factor (TNF) inhibitors. The influence of biological agents, however, remains unclear in Japanese RA patients.
Objectives To investigate the risk of NTM infection and exacerbation in Japanese RA patients treated with biological agents.
Methods We retrospectively reviewed the medical records of all RA patients under regular follow up at our institution in December 2012. They were observed through October 2014. NTM was diagnosed according to the criteria proposed by the American Thoracic Society and Infectious Diseases Society of America although some cases were diagnosed by chest physicians. Exacerbations of NTM in this study were defined as clinical or radiographic exacerbations so that chest physicians decided to change therapy for NTM to control the activity of NTM.
Results This study included 1649 patients. At baseline, 27 patients had already been diagnosed as NTM and 7 were newly diagnosed during observation period. The prevalence rate and incidence rate (95% confidence interval [CI]) of NTM in RA patients was 1637 (1025-2250) per 100,000 patients and 250 (7-435) per 100,000 patient-years, respectively. Baseline characteristics are shown in Table. Of 1622 patients without NTM and of 27 patients with NTM, 762 and 7 patients had been treated with at least 1 biological agent before December 2012 or NTM diagnosis, respectively (Table). Prior use of biological agents was not associated with increased risk of NTM, rather associated with significantly decreased risk (odds ratio [OR], 0.40; 95% CI, 0.16-0.96; p=0.049). Among biological agents, TNF inhibitors were not associated with increased risk of NTM, either (OR, 0.43; 95% CI, 0.16-1.13; p=0.10). Of all 34 patients diagnosed as NTM, 29 (85%) were female. The age at NTM diagnosis (median, interquartile range [IQR]) was 63 (54.8-70.3) years old. The median (IQR) disease duration of RA at the time of NTM diagnosis was 9.7 (6.3-20.4) years, with 3 patients who were diagnosed as RA during the course of NTM. NTM species included M. avium complex in 32 patients, M. kansasii in 1 patient, and M. abcsessus in 1 patient. Radiographic features included 27 nodular/bronchiectatic (NB) disease, 2 fibrocavitary (FC) disease, 7 NB+FC disease and 3 other disease. After diagnosed as NTM, 12 patients were treated with biological agents; 5 patients by etanercept (ETN); 2 by tocilizumab (TCZ); and 5 by abatacept (ABT). Four of them experienced exacerbation (1 with ETN, 2 with TCZ, and 1 with ABT, respectively). Three of the other 22 receiving non-biological therapy also experienced exacerbation (methotrexate, salazosulfapyridine, and tacrolimus, respectively). Treatment with biological agents was not associated with exacerbation, either (OR, 3.2; 95% CI, 0.57-17.5; p=0.21). Respiratory failure and death was not detected during observation period among patients with NTM.
Conclusions Japanese patients with RA showed high prevalence and incidence rate of NTM infection and biological agents did not increase the risk of NTM infection or the exacerbation of NTM. We should be careful when treating RA patients with NTM regardless of therapy.
Disclosure of Interest H. Takei: None declared, N. Nishina: None declared, K. Suzuki Grant/research support from: Eisai.Co.Ltd. and Bristol-Myers Squibb Company, K. Yamaoka Consultant for: Pfizer, Chugai Pharma, Mitsubishi-Tanabe Pharma, Takeda Industrial Pharma, GlaxoSmithKline, Nippon Shinyaku, Eli Lilly, Janssen Pharma, Eisai Pharma, Astellas Pharma and Actelion Pharmaceuticals., Speakers bureau: Pfizer, Chugai Pharma, Mitsubishi-Tanabe Pharma, Takeda Industrial Pharma, GlaxoSmithKline, Nippon Shinyaku, Eli Lilly, Janssen Pharma, Eisai Pharma, Astellas Pharma and Actelion Pharmaceuticals., 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., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co.,Ltd., Celtrion, Nipponkayaku Co.Ltd