Risk factors for serious infection during treatment with cyclophosphamide and high‐dose corticosteroids for systemic lupus erythematosus

Abstract

Objective. To determine risk factors for serious infection during treatment with cyclophosphamide (CYC) and high-dose corticosteroids in systemic lupus erythematosus (SLE).Methods. Records of 100 SLE patients who had received CYC were examined for documentation of serious infections that occurred during CYC therapy and the subsequent 3 months.Results. Infection occurred in 45 of 100 patients during CYC therapy. Patients with infection were more likely to have multiple organ disease (4Wo versus 2Wo; P = OM), a lower nadir in the white blood cell (WBC) count (2,818 versus 3,558 celldpl; P = 0.02), and a higher maximum corticosteroid dose (195 versus 73 mg; P S 0.01) than patients without infection. Infection occurred with equal prevalence in those who received intravenous (IV) (39%) or oral (40%) CYC, but was more common with use of sequential IV and oral therapy (68%). By multivariate analysis, the strongest association with infection was a WBC nadir $3,000 cells/pl (odds ratio [OR] 2.8, 95% confidence interval [95% CI] 1.4-5.5) and use of sequential IV and oral CYC (OR 23, 95% CI 12-43), Infection occurred in more CYC-treated patients taking concomitant steroids than in those treated with high-dose steroids alone (45% versus 12%; P = 0.001). Fatal and opportunistic infections during CYC therapy were associated with a low WBC nadir and a high ma)rimum corticosteroid dose.Conelusion. Submitted for publication July 12, 1995; accepted in revised form March 11, 1996. the treatment regimen. The likelihood of infection in this setting is enhanced by CYC-induced reductions in the total WBC count C3, OOO cells/pl and by sequential IV and oral therapy. Both of these factors may be indicators of aggressive cytotoxic treatment, underscoring the need for close observation during treatment to minimize the risk of serious infection.

Management of infection in systemic lupus erythematosus

“…Prednisone treatment, even at moderate doses, increases the risk, whilst antimalarials have a protective effect [13]. In detail, it was shown that the prednisone dose at the time of the event had a facilitating effect on infections, in agreement with previous studies [9], [10] and [11]. Moreover, it is worthy of note that the median dose of patients with major infections was only 7.5 mg day−1, with an 11-times higher risk of suffering a serious infection for each increase of 10-mg day−1 prednisone.…”

“…Several studies have analysed the prevalence and associated clinical and laboratory features of infection in SLE *[8], [9], [10] and [11]. Common themes are medications, including use of steroids and/or cyclophosphamide or high-disease activity as measured by the SLE Disease Activity Index [12].…”

Is Newer Safer? Adverse Events Associated with First-Line Therapies for ANCA-Associated Vasculitis and Lupus Nephritis

“…In one AAV cohort of 158 patients (most of whom were treated with CYC and steroids), 46% of patients experienced a severe infection during a mean follow-up of 8 years (1). CYC with steroids has also been associated with an increased risk of infections in patients with lupus (32%-45% with combination therapy compared with 7%-12% with steroids alone) (10,18,19). In the induction trials for AAV discussed earlier, number and incidence of infections did not differ between treatment groups, (Table 1), and in lupus nephritis induction trials, only the trial by Ginzler et al demonstrated a difference in severe infections (4% in the CYC group versus 1% in the MMF group), with identical percentages of patients experiencing other infections (Table 2).…”

Recent‐onset systemic lupus erythematosus complicated by acute respiratory failure

“…Cyclophosphamide is often used to treat severe organ-threatening flares of systemic autoimmune disease, including severe SLE, and it is known to increase the potential risk for infections, including PCP. In 1 retrospective study of 100 SLE patients treated with cyclophosphamide, the incidence of PCP was elevated at 3% (27); however, it is not surprising given the severity of illness warranting cyclophosphamide that all of these patients were concurrently receiving corticosteroids. One study that included patients with CTD where the majority (73%) was not receiving concurrent corticosteroids is the Scleroderma Lung Study, in which 79 patients with systemic sclerosis-associated ILD were treated with cyclophosphamide (28).…”