Intravenous cyclophosphamide (CYC) pulse therapy may be considered a treatment option for diffuse cutaneous systemic sclerosis (dcSSc) either after methotrexate has failed or as first-line therapy, according to study results published in Rheumatology.1

Recent studies have shown a significant improvement in skin thickening of patients who received CYC orally,2 but the effect of intravenous CYC on skin involvement remains unclear.

Researchers conducted a retrospective, longitudinal, observational study to evaluate the extent of skin thickening over 12 months of intravenous CYC (750 mg/m2) in SSc and to identify factors that predict response to therapy. Patients were classified as having dsSSc or limited cutaneous SSc (lcSSc) based on the Leroy and Medsger criteria.

A total of 143 patients with SSc receiving intravenous CYC between 2004 and 2016 were included in the study. Skin involvement was accessed with the modified Rodnan Skin score (mRSS) at baseline, and at 6, 12, 24, and 36 months by trained rheumatologists as part of routine care. Data from patients with baseline and ≥1 follow-up measurement were included in the study. Clinically relevant response was defined as a decrease in mRSS of 5 points and 25% from baseline at month 12. Researchers developed a prediction model for response at 12 months using logistic regression with baseline variables, including age and sex, and response at 6 months as possible predictors.


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According to response criteria, 43% (n=42) of patients with early dcSSc who received intravenous CYC pulse therapy had a clinically significant response to treatment at month 12. The mRSS decreased -3.9 points (95% CI, -5.4 to -2.5 points) at 12 months in the dcSSc group, whereas the lcSSc group remained stable, with a mean change of 0.3 points (95% CI, -0.7 to 1.3 points).

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Furthermore, researchers indicated that patients with dcSSc who did not respond to treatment by month 6 predicted a nonresponse by month 12 (odds ratio, 37.1; 95% CI, 4.5-306.4).

Study limitations included the lack of a control group and mRSS for every patient at all timepoints.

“Data show that after 6 months of therapy, a decision can be made according to the response to therapy regarding whether to continue [intravenous] CYC pulse therapy or to choose another therapy (such as MMF or ASCT) if patients are eligible,” the researchers concluded.

References

1. Kersten BE, den Broeder N, van den Hoogen FHJ, et al. Treatment with cyclophosphamide i.v. pulse therapy is an option for effective treatment of skin fibrosis in patients with early systemic sclerosis [published online February 10, 2020] Rheumatology. doi: 10.1093/rheumatology/kez487

2. Namas R, Tashkin DP, Furst DE, et al. Efficacy of mycophenolate mofetil and oral cyclophosphamide on skin thickness: post hoc analyses from two randomized placebo-controlled trials. Arthritis Care Res. 2018;70:439-444.