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Do patients on biologic drugs for rheumatic disease need PCP prophylaxis?

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Pneumocystis jirovecii (previously carinii) pneumonia (PCP) is rare in patients taking biologic response modifiers for rheumatic disease.1–10 However, prophylaxis should be considered in patients who have granulomatosis with polyangiitis or underlying pulmonary disease, or who are concomitantly receiving glucocorticoids in high doses. There is some risk of adverse reactions to the prophylactic medicine.1,11–21 Until clear guidelines are available, the decision to initiate PCP prophylaxis and the choice of agent should be individualized.

THE BURDEN OF PCP

Table 1. Biologic agents used for rheumatic disease
PCP is a life-threatening opportunistic infection. Common causes of immunosuppression are advanced human immunodeficiency virus (HIV) infection, hematologic malignancy, anti-rejection drugs, chemotherapy, glucocorticoid therapy, and other immunosuppressive drugs. Here, we focus on the risk of PCP with immunomodulatory biologic drugs used for rheumatic disease that deplete B cells or inhibit T-cell activation, cytokine production, or cytokine function (Table 1).22

In a meta-analysis23 of 867 patients who developed PCP and did not have HIV infection, 20.1% had autoimmune or chronic inflammatory disease and the rest were transplant recipients or had malignancies. The mortality rate was 30.6%.

PHARMACOLOGIC RISK FACTORS FOR PCP

Treatment with glucocorticoids

Treatment with glucocorticoids is an important risk factor for PCP, independent of biologic therapy.

Calero-Bernal et al11 reported on 128 patients with non-HIV PCP, of whom 114 (89%) had received a glucocorticoid for more than 4 weeks, and 98 (76%) were currently receiving one. The mean daily dose was equivalent to 27.73 mg of prednisone per day in those on glucocorticoids only, and 21.34 mg in those receiving glucocorticoids in combination with other immunosuppressants.

Park et al,12 in a retrospective study of Korean patients treated for rheumatic disease with high-dose glucocorticoids (≥ 30 mg/day of prednisone or equivalent for more than 4 weeks), reported an incidence rate of PCP of 2.37 per 100 patient-years in those not on prophylaxis.

Other studies13,14 have also found a prednisone dose greater than 15 to 20 mg per day for more than 4 weeks or concomitant use of 2 or more disease-modifying antirheumatic drugs to be a significant risk factor.13,14

Tumor necrosis factor alpha antagonists

A US Food and Drug Administration review1 of voluntary reports of adverse drug events estimated the incidence of PCP to be 2.3 per 100,000 patient-years with infliximab and 1.6 per 100,000 patient-years with etanercept. In most cases, other immunosuppressants were used concomitantly.1

Postmarketing surveillance2 of 5,000 patients with rheumatoid arthritis showed an incidence of suspected PCP of 0.4% within the first 6 months of starting infliximab therapy.

Komano et al,15 in a case-control study of patients with rheumatoid arthritis treated with infliximab, reported that all 21 patients with PCP were also on methotrexate (median dosage 8 mg per week) and prednisolone (median dosage 7.5 mg per day).

PCP has also been reported after adalimumab use in combination with prednisone, azathioprine, and methotrexate, as well as with certolizumab, golimumab, tocilizumab, abatacept, and rituximab.3–6,24–26

Rituximab

Calero-Bernal et al11 reported that 23% of patients with non-HIV PCP who were receiving immunosuppressant drugs were on rituximab.

Alexandre et al16 performed a retrospective review of 11 cases of PCP complicating rituximab therapy for autoimmune disease, in which 10 (91%) of the patients were also on corticosteroids, with a median dosage of 30 mg of prednisone daily. A literature review of an additional 18 cases revealed similar findings.

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