Dermatology & Plastic Surgery Institute Outcomes

It is standard medical practice for immunosuppressed patients to receive prophylaxis against Pneumocystis jirovecii pneumonia (PCP), for which trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line treatment.¹ Although TMP-SMX is relatively contraindicated in patients taking methotrexate (MTX) due to synergistic toxicities, little is known about the safety of TMP-SMX dosing for PCP prophylaxis in combination with MTX.²

Cleveland Clinic clinicians identified 100 consecutive patients prescribed TMP-SMX for PCP prophylaxis concurrently with MTX for ++>++1 month in 2017 for chronic inflammatory/autoimmune diseases. All patients took one double-strength 800 mg/160 mg tablet of TMP-SMX, 3 times weekly for PCP prophylaxis.

Six of the 100 patients experienced adverse events triggering discontinuation of combination therapy. Discontinuation reasons included transaminitis (N = 4) and/or leukopenia (N = 2). One patient discontinued due to cognitive deficits, fatigue, and headaches. Four patients who discontinued combination therapy had underlying hepatic abnormalities. Two of the 6 patients with significant adverse events discontinued both MTX and TMP-SMX, 3 stopped MTX but continued TMP-SMX, and 1 patient stopped TMP-SMX but continued MTX. In all patients, liver function tests were normal at combination therapy initiation and normalized following discontinuation.

Both patients who developed leukopenia had normal baseline white blood cell counts (WBC). One patient developed leukopenia (WBC = 1.74 k/uL) with absolute lymphopenia (0.37 k/uL) and neutropenia (1.24 k/uL), all of which resolved following combination therapy discontinuation. The second patient had leukopenia (WBC = 2.94 k/uL) and absolute lymphopenia (0.61 k/uL), both of which resolved after discontinuation.

MTX dose, treatment duration, and folic acid/leucovorin dose were not significantly different in patients with or without adverse events leading to combination therapy discontinuation. No patient contracted PCP or had an adverse event leading to end-organ damage.

This study represents one of the largest to document combination MTX and PCP prophylaxis-dosed TMP-SMX therapy appears both successful and well-tolerated in patients with chronic inflammatory/autoimmune diseases.³ The findings suggest baseline CBCs and CMPs may be useful in identifying at-risk patients for adverse effects if placed on MTX and TMP-SMX combination therapy. In patients with underlying liver abnormalities and/or CBC abnormalities, alternative PCP prophylaxis strategies should be considered.