Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics, based on risk factors found in a retrospective study

Arthritis Research & Therapy, Feb 2014

Introduction Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections in patients undergoing immunosuppressive therapy. In this article, we discuss risk factors for PCP development in patients with rheumatoid arthritis (RA) during the course of biologic therapy and describe a prophylactic treatment for PCP with trimethoprim/sulfamethoxazole (TMP/SMX). We also evaluate the effectiveness and safety of the treatment. Methods We retrospectively analyzed 702 RA patients who received biologic therapy and compared the characteristics of patients with vs. without PCP to identify the risk factors for PCP. Accordingly, we analyzed 214 patients who received the TMP/SMX biologic agents as prophylaxis against PCP at the start of treatment to evaluate their effectiveness and safety. Results We identified the following as risk factors for PCP: age at least 65 years (hazard ratio (HR) = 4.37, 95% confidence interval (CI) = 1.04 to 18.2), coexisting pulmonary disease (HR = 8.13, 95% CI = 1.63 to 40.0), and use of glucocorticoids (HR = 11.4, 95% CI = 1.38 to 90.9). We employed a protocol whereby patients with two or three risk factors for PCP would receive prophylactic treatment. In the study with 214 patients, there were no cases of PCP, and the incidence of PCP was reduced to 0.00 per 100 person-years compared with that before the procedure (0.93 per 100 person-years). There were no severe adverse events induced by the TMP/SMX treatment. Conclusions RA patients with two or three risk factors for PCP who are receiving biologic therapy can benefit from safe primary prophylaxis.

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Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics, based on risk factors found in a retrospective study

Katsuyama et al. Arthritis Research & Therapy Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics, based on risk factors found in a retrospective study Takayuki Katsuyama 0 Kazuyoshi Saito 0 Satoshi Kubo 0 Masao Nawata 0 Yoshiya Tanaka 0 0 First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health , 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555 , Japan Introduction: Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections in patients undergoing immunosuppressive therapy. In this article, we discuss risk factors for PCP development in patients with rheumatoid arthritis (RA) during the course of biologic therapy and describe a prophylactic treatment for PCP with trimethoprim/sulfamethoxazole (TMP/SMX). We also evaluate the effectiveness and safety of the treatment. Methods: We retrospectively analyzed 702 RA patients who received biologic therapy and compared the characteristics of patients with vs. without PCP to identify the risk factors for PCP. Accordingly, we analyzed 214 patients who received the TMP/SMX biologic agents as prophylaxis against PCP at the start of treatment to evaluate their effectiveness and safety. Results: We identified the following as risk factors for PCP: age at least 65 years (hazard ratio (HR) = 4.37, 95% confidence interval (CI) = 1.04 to 18.2), coexisting pulmonary disease (HR = 8.13, 95% CI = 1.63 to 40.0), and use of glucocorticoids (HR = 11.4, 95% CI = 1.38 to 90.9). We employed a protocol whereby patients with two or three risk factors for PCP would receive prophylactic treatment. In the study with 214 patients, there were no cases of PCP, and the incidence of PCP was reduced to 0.00 per 100 person-years compared with that before the procedure (0.93 per 100 person-years). There were no severe adverse events induced by the TMP/SMX treatment. Conclusions: RA patients with two or three risk factors for PCP who are receiving biologic therapy can benefit from safe primary prophylaxis. - Introduction A paradigm shift in the treatment of rheumatoid arthritis (RA) has been brought about by the introduction of biologic agents. Special attention should be given to opportunistic infections in RA patients treated with biologics. The strict postmarketing surveillance of an anti-tumor necrosis factor (anti-TNF) agent, etanercept (ETN), in Japan showed that 1,206 (8.7%) of 13,894 patients developed infections and 334 patients (2.4%) developed severe infections [1]. Authors of several reports have identified severe infections in patients receiving other biologics and have indicated the significance of prophylaxis for opportunistic infections in RA patients. Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections, and it can lead to potentially lethal respiratory dysfunction in patients with HIV infection. It is also observed in patients with autoimmune diseases undergoing immunosuppressive treatment [2]. Takabayashi et al. reported that PCP developed in 9 (1.2%) of 761 patients with autoimmune diseases [3]. It has been demonstrated that PCP in non-HIV patients is more rapidly progressive and fatal than in it is in HIV patients [4]. Several cases of PCP in Crohns disease patients who were receiving infliximab (IFX) have been reported [5-7]. Authors of other reports have shown that PCP developed in patients with RA during the course of biologic therapy. Postmarketing surveillance in Japan revealed that 22 (0.44%) of 5,000 patients receiving IFX [8] and 25 (0.18%) of 13,894 patients receiving ETN developed PCP [1]. It is well-known that HIV patients with a CD4+ cell count less than 200 cells/mm3 are likely to develop PCP and that the most common identifiable risk factor for developing PCP in patients with autoimmune disease or malignancy is the use of glucocorticoids [9,10]. However, there have been few published reports on the risk factors for PCP development in patients with RA who are receiving biologics, possibly because of the low incidence and small degree of recognition of PCP in Western countries. In this study, we first retrospectively analyzed patients with RA who had started treatment with biologic agents (TNF or interleukin 6 (IL-6) inhibitors) before September 2009 to identify the risk factors for PCP development and determined the primary prophylactic procedure. The prophylactic procedure was applied to RA patients who started treatment with biologics between October 2009 and September 2010, then we retrospectively analyzed these cases to estimate the effectiveness and safety of the procedure. Methods First cohort study to detect risk factors for developing Pneumocystis pneumonia We retrospectively analyzed 702 traceable patients with RA who had started treatment with biologic agents between April 2005 and September 2009 in the First Department of Internal Medicine, University of Occupational and Environmental Health ( (...truncated)


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Takayuki Katsuyama, Kazuyoshi Saito, Satoshi Kubo, Masao Nawata, Yoshiya Tanaka. Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics, based on risk factors found in a retrospective study, Arthritis Research & Therapy, 2014, pp. R43, 16, DOI: 10.1186/ar4472