Background An increased risk of respiratory infections among rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ) has been known through clinical trials and by postmarketing surveillance. So far, little data is available from detailed analysis of respiratory infections among RA patients with long-term follow-up of TCZ treatment in daily clinical practice.
Objectives To study the frequency, degree of laboratory data of respiratory infections, and the frequency of patients who discontinued TCZ because of respiratory infection among RA patients treated with TCZ for average 2.7 years.
Methods One hundred and seventeen RA patients (mean age 56±12.5 years: 85% women) have been treated with TCZ (8mg/kg) for more than 24 weeks in our hospital after June 2008. Respiratory infection (bronchitis, pneumonia and tuberculosis) was detected by chest radiography, pulmonary CT and clinical records indicating the use of antibiotics. Frequency of respiratory infections, the titer of WBC and C-reactive protein (CRP) and cessation period of TCZ were described.
Results 117 RA patients were treated with TCZ. Mean treatment duration was 2.66±1.43 years [7 months∼5.5 years]. Mean prednisolone use was 5.1±5.2 mg and 59.4% were concomitantly used methotrexate at the beginning of the start of TCZ. Mean baseline DAS28-CRP was 4.55±1.26. Respiratory problems occurred in 23 patients. Bronchitis occurred in 13 cases among 11 patients, pneumonia occurred in 12 cases for 10 patients, 1 patient was considered as methotrexate-induced pneumonia and upper respiratory tract tuberculosis was found in 1 patient. Mean WBC count and CRP for bronchitis patients were 6,650±3,470/mm3 and 2.4±3.0 mg/L, respectively. Mean WBC count and CRP for pneumonia patients were 10,420±6,780/mm3 and 10.3±20.8 mg/L, respectively. The titer of CRP was normal for the entire observation period for respiratory problems in 84.6% of bronchitis cases, and 41.7% of pneumonia cases. All bronchitis and pneumonia cases responded to antibiotics. Admission to hospital was necessary only for pneumonia cases (75%). In most of the cases restart of TCZ was possible. In cases of pneumonia, mean cessation period of TCZ was average 4.8 weeks [0∼18 weeks, median 3 weeks]. TCZ was withdrawn in 2 cases, that is the upper respiratory tract tuberculosis case and a repeated pneumonia case.
Conclusions Masked early symptoms and laboratory abnormalities of pneumonia in patients with RA during TCZ treatment are sometimes described in literature. We confirmed this fact by following patients for average 2.7 years. Our analyses, composed of 117 patients, showed about half of the pneumonia patients of RA with TCZ treatment did not show elevation of CRP for the entire period of pneumonia. These facts indicate that appropriate treatment for respiratory infections among RA patients treated with TCZ is linked to putting diagnostic weight on symptoms and careful image examination.
Yanagawa Y, et al. BMJ Case Rep. published online 23 May 2012.
Acknowledgements The authors thank Ms. Ayumi Kondou for her excellent secretarial assistance.
Disclosure of Interest None declared