Clinical Factors Associated With Pneumocystis Pneumonia Despite Its Primary Prophylaxis: When to Stop Prophylaxis?

Abstract

Objective: Although previous studies show that primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is effective in patients with rheumatic diseases receiving immunosuppressive treatment, there is limited evidence regarding the optimal timing for prophylaxis withdrawal. This study aimed to identify the risk factors for PJP despite prophylaxis and provide evidence for an optimal prophylaxis schedule.

Methods: This case-control study included 1,294 prophylactic episodes in 1,148 patients with rheumatic disease who received immunosuppressants and prophylactic trimethoprim-sulfamethoxazole (TMP-SMX). The primary outcome was a one-year incidence of PJP. A Cox proportional hazards model with least absolute shrinkage and selection operator was used to evaluate clinical factors associated with outcomes.

Results: During 1,174 person-years of observation, 10 cases of PJP were identified, with an incidence rate of 0.85 per 100 person-years. The mean ± SD duration of TMP-SMX prophylaxis was 181.9 ± 128.7 days. Except in one case, PJP occurred after discontinuation of TMP-SMX, with a median (interquartile range [IQR]) interval of 117.0 (86.0-161.0) days. The dose of glucocorticoids at the time of TMP-SMX discontinuation was significantly higher in the PJP group relative to the control group (median [IQR]: 22 [20-40] vs 10 [5-15] mg). Discontinuing TMP-SMX while on a glucocorticoid dose >12.5 mg/day of prednisone equivalent significantly increased the risk of PJP (adjusted hazard ratio: 13.84; 95% confidence interval, 1.71-111.80). There were 63 cases of adverse events during the observation period, and 10 (15.9%) were attributed to TMP-SMX with probable causality.

Conclusion: Tapering glucocorticoids with 12.5 mg/day of prednisone equivalent could be a reasonable timepoint to initiate the withdrawal of PJP prophylaxis in patients with rheumatic diseases.

Figure 1

Density plot showing the dose of GC at the time of trimethoprim‐sulfamethoxazole discontinuation in the PJP and the control group. GC, glucocorticoid; PJP, Pneumocystis jirovecii pneumonia. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.43167/abstract.

Figure 2

Kaplan–Meier curve indicating the Pneumocystis jirovecii pneumonia incidence stratified by the dose of GC at the time of discontinuing TMP‐SMX. GC, glucocorticoid; TMP‐SMX, trimethoprim‐sulfamethoxazole.