Clinical characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with rheumatoid arthritis receiving adalimumab: a retrospective review and case–control study of 17 patients

Abstract

Objectives To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab.

Methods We conducted a multicenter, retrospective, case–control study to compare RA patients treated with adalimumab with and without PCP. Data from 17 RA patients who were diagnosed with PCP and from 89 RA patients who did not develop PCP during adalimumab treatment were collected.

Results For the PCP patients, the median age was 68 years old, with a median RA disease duration of eight years. The median length of time from the first adalimumab injection to the development of PCP was 12 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 5.0 mg/day and 8.0 mg/week, respectively. The patients with PCP were significantly older (p < 0.05) and had more structural changes (p < 0.05) than the patients without PCP. Computed tomography of the chest revealed ground-glass opacity without interlobular septal boundaries in the majority of the patients with PCP. Three PCP patients died.

Conclusions PCP may occur early in the course of adalimumab therapy in patients with RA. Careful monitoring, early diagnosis, and proper management are mandatory to secure a good prognosis for these patients.

Keywords::

• Adalimumab
• Pneumocystis jirovecii pneumonia
• Rheumatoid arthritis
• TNF antagonist

Acknowledgments

We would like to thank Drs. Yoshihisa Nojima (Gunma University Graduate School of Medicine), Takeo Sakurai (Inoue Hospital), Shoichi Ozaki (St. Marianna University School of Medicine), Kimihiro Kida (Nagara Orthopaedic Clinic), Tomio Shimizu (Chibune General Hospital), Toshio Tanaka (Osaka University Graduate School of Medicine), Motoaki Kin (Higashihiroshima Memorial Hospital), Atsuko Imai (Ichiban-cho Clinic for the Rheumatic Diseases), Masakazu Kondo (Kondo Clinic for Rheumatism and Orthopaedics), Eiichi Suematsu (National Hospital Organization Kyushu Medical Center), and Tamami Yoshitama (Yoshitama Rheumatoid Arthritis and Internal Medicine Clinic) for their contributions to the face-to-face meeting of this study.

Conflict of interest

Fumikazu Sakai has received research funds form the Japanese Ministry of Labor, Health and Welfare, Japanese Ministry of Environment, Ministry of Education, Culture, Sports, Science and Technology in Japan, LTT Bio Ltd., Eisai Co. Ltd., Daiichi-Sankyo Co. Ltd., Kovidien Co., and Bayer Co. Ltd., and has received consulting fees form Takeda Pharmaceuticals, Chugai Pharmaceuticals, Rosche, MSD, Astra-Zeneca, Merk Serrono, Pfizer, Bayer, Jansen Pharma, and has received lecture fees form Daiichi Sankyo Co. Ltd., Eizai Co. Ltd., Kyorin Pharmaceuticals, Shionogi Pharmaceuticals. Yoshiya Tanaka has received consulting fees, speaking fees, and/or honoraria from Mitsubishi-Tanabe Pharma, Abbott Japan, Chugai Pharma, Janssen Pharma, Eisai Pharma, Santen Pharma, Pfizer, Astellas Pharma, Daiichi-Sankyo, GlaxoSmithKline, Astra-Zeneca, Otsuka Pharma, Actelion Pharma Japan, and Eli Lilly Japan, and has received research grant support from Bristol-Myers Squibb, MSD, Chugai Pharma, Mitsubishi-Tanabe Pharma, Astellas Pharma, Abbott Japan, Eisai Pharma, and Janssen Pharma. Masayoshi Harigai and Nobuyuki Miyasaka have received research grants from Abbott Japan, Astellas, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi-Tanabe Pharma Corp., Novartis Pharma K.K., Takeda Pharmaceutical Co. Ltd., and Wyeth K.K. (now Pfizer). There are no other competing interests for the other authors regarding this article. This work was supported by a grant-in-aid for scientific research (KAKENHI) from the Japan Society for the Promotion of Science to R.K. (#19590530), M.H. (#20390158) and M.T. (#23590171), and by a grant-in-aid from the Ministry of Health, Labor and Welfare, Japan (H19-meneki-ippan-009 to N.M. and M.H and 22-meneki-ippann-001 to M.H.). This work was also supported by the Global Center of Excellence (GCOE) program “International Research Center for Molecular Science in Tooth and Bone Diseases” (to N.M.).