Pneumocystis pneumonia (PCP) prophylaxis based on published prophylaxis criteria instead of physician assessment alone decreased the PCP incidence in patients with rheumatoid arthritis (RA) on biologic or targeted-synthetic DMARDs (b/tsDMARDs), study data published in Rheumatology reported. Sulfamethoxazole/trimethoprim (SMX/TMP) was also found to be more effective for PCP prophylaxis than pentamidine inhalation, even when given a lower-than-standard dose.

Investigators collected data on patients from Japan’s FIRST registry, consisting of patients with RA enrolled in a long-term observational study at the point of a new b/tsDMARD prescription or a switched b/tsDMARd prescription. Cohort 1 included patients who received PCP prophylaxis based on physicians’ assessments when starting or switching to treatment with b/tsDMARDs from August 2003 to September 2009. Cohort 2 included patients who received strategic PCP prophylaxis, that is, prophylaxis based on published criteria in addition to physicians’ assessments, after October 2009. PCP prophylaxis included either oral SMX/TMP 80-560 mg once weekly, pentamidine inhalation 300 mg per visit, or oral atovaquone 1500 mg once daily. The main outcome of interest was the incidence of PCP in each cohort.

There were 3,787 patients with RA from the FIRST registry, 807 in cohort 1 and 2,980 in cohort 2. In cohort 1, 117 patients underwent PCP prophylaxis: 113 with SMX/TMP and 4 with pentamidine. There were 13 patients who developed PCP, 1 who received prophylaxis at baseline and 12 who did not. In cohort 2, 1,512 patients underwent PCP prophylaxis, 1,411 with SMX/TMP, 98 with pentamidine, and 3 with atovaquone. There were 13 patients who developed PCP, 7 who received prophylaxis at baseline and 6 who did not.


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Strategic PCP lowered the incidence of PCP from 0.51/100 person-year (py) to 0.21/100 py (risk ratio, 0.42; 95% CI, 0.20-0.91; Log rank P =.02).

The 8 patients who developed PCP despite prophylaxis at baseline were either treated with pentamidine inhalation (n=5) or had no treatment at the time of PCP onset (n=3). There were no PCP cases for patients treated with SMX/TMP prophylaxis (P <.0001). Since SMX/TMP is known to cause numerous adverse events, investigators de-escalated the dose from 454 mg/week in 2004 to 275 mg/week in 2019. PCP incidence still decreased chronologically from 3.4/100 py in 2004 to 0/100 py in 2019.

A sub-analysis of 929 patients from both cohorts who did not receive prophylaxis showed that old age, BMI, coexisting lung disease, low lymphocyte count, and low serum IgG levels increased the risk of developing PCP. Concomitant use of glucocorticoids was not a predictor of PCP, despite the fact that current PCP prophylaxis criteria includes the use of oral glucocorticoids.

There were no severe adverse events due to PCP prophylaxis in either cohort, it was reported. The study was limited by the fact that PCP rates vary globally.

In light of the effective lower SMX/TMP dose and the lack of severe adverse events, “beyond-necessity-provision of PCP prophylaxis with dose de-escalation is acceptable and rather seems a better clinical practice,” the study authors wrote.

Investigators also pointed out that PCP prophylaxis criteria are “less than ideal today” since the rate of glucocorticoid use dropped in cohort 2 and glucocorticoid use was not predictive of PCP risk in this study. They revised the criteria by only including the predictive variables for PCP risk, listed above.

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Sonomoto K, Tanaka H, Nguyen TM, et al. Prophylaxis against pneumocystis pneumonia in rheumatoid arthritis patients treated with b/tsDMARDs: Insights from 3,787 cases in FIRST registry. Rheumatology. Published online August 11, 2021. doi:10.1093/rheumatology/keab647