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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.
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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)