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Is PJP Prophylaxis Indicated in Patients With Giant Cell Arteritis or Polymyalgia Rheumatica?

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Results of a recent study showed that the risk of pneumocystis jiroveci pneumonia (PJP) is low in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), therefore discouraging the routine prescribing of PJP prophylaxis for this patient population.

Pneumocystis jiroveci pneumonia (PJP) is an opportunistic fungal infection that typically affects immunocompromised patients. Guidelines recommend PJP prophylaxis in patients with ANCA-associated vasculitis,1 but no formal recommendations exist for giant cell arteritis (GCA) or polymyalgia rheumatica (PMR). Studies have demonstrated antibiotic prophylaxis reduces incidence of PJP in immunocompromised patients, but little data has evaluated the role of prophylaxis in GCA or PMR. The authors of a recent study by Natalie Anumolu et al sought to answer the question of PJP incidence in this population, given patients with GCA/PMR often receive prolonged courses of steroids, particularly GCA with high doses and often concomitant immunosuppression with tocilizumab.2

In this study, authors utilized a United States-based electronic health records database (TriNetX), including de-identified information from 54 healthcare organizations and over 86 million patients across the United States. The cohort identified patients with GCA and PMR, using ICD-9/ICD-10 diagnosis codes, who had a glucocorticoid prescription. Patients were excluded if they had human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), any reported transplant, or leukemia. They also excluded patients with any PJP code within a specified time period surrounding the index date (defined as first glucocorticoid prescription, required to occur within 30 days after first diagnosis code). The team extracted demographic data, medications used, and type of prophylaxis as well as medical comorbidities and assessed incidence rate of PJP.To identify other cases of PJP, a systematic review was also performed.

The study found a total of 1168 incident cases of GCA and over 15,575 incident cases of PMR.During follow-up, steroid-sparing agents included tocilizumab (9.5% GCA, 0.7% PMR) and methotrexate (7.1% GCA, 6.7% PMR). A minority of patients received prophylaxis, including trimethoprim/sulfamethoxazole (TMP/SMX) (6.1% GCA, 1.6% PMR), atovaquone (0.4% GCA, 0.1% PMR), or dapsone (0.6% GCA, 0% PMR) for presumed PJP prophylaxis. Among 1168 patients with GCA, there were no cases, positive tests or hospitalizations for PJP (0/1,000 person-years). Among 15,575 patients with PMR, there was 1 case of PJP within 6 months and 1 positive case within 12 months, with no hospitalizations (0.07/1,000 person-years). Evaluating the systematic reviews, in GCA they found 28 total cases of PJP with 4 cases of mortality; in PMR, there were 4 cases of PJP prophylaxis and no deaths reported.

Combining results of the cohort study and systematic review, the authors conclude PJP infection occurred rarely among patients with GCA or PMR. They noted their cohort study identified no cases of PJP in those with GCA and only 5 cases in those with PMR, which may approximate rates observed in the general population. Patients with GCA/PMR often require high cumulative glucocorticoid dosage for treatment, and they hypothesize a few reasons for why the incidence rate of PJP is not higher, including: 1) medications do not affect T-cells to the same degree active HIV does and 2) patients with GCA/PMR lack disease-mediated lung disease. The authors noted some limitations, such as reasons prophylaxis treatment not being listed in some cases and having to be inferred, and lack of granular data on corticosteroid dosing. Additionally, I will note the low percentage of patients on tocilizumab or methotrexate in the GCA cohort. It is possible the rate of PJP incidence may vary in those on prednisone monotherapy versus prednisone in combination with other immunosuppressant.

Ultimately, as rheumatologists we are balancing control of underlying disease and risks of immunosuppressive treatment. This data suggests the risk of PJP in patients with GCA or PMR are low, and it is important to recognize the potential range of adverse events from PJP prophylaxis are vast, including methemoglobinemia and agranulocytosis. Given these findings, the authors concluded “these data do not support routine prescribing of PJP prophylaxis for patients with GCA or PMR.”

References

  1. Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, et al. American college of rheumatology/vasculitis foundation guideline for the management of antineutrophil cytoplasmic antibody–associated vasculitis. Arthritis Care Res 2021; 73:1088–105.
  2. Anumolu N, Henry K, Sattui SE, Putman M. Is there a role for Pneumocystis jiroveci pneumonia prophylaxis in giant cell arteritis or polymyalgia rheumatica? Seminars in Arthritis and Rheumatism 2023; 58:152154.

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