Immunosuppressants Effective for Early Diffuse Cutaneous Systemic Sclerosis Treatment

Immunosuppressants reduced modified Rodnan skin scores in patients with early diffuse cutaneous systemic sclerosis (dcSSc) compared with patients who were not using immunosuppressants, according to recent research from the European Scleroderma Observational Study (ESOS) published in the Annals of the Rheumatic Diseases.

“[T]here were no significant differences in outcome between the four treatment protocols (methotrexate, MMF [mycophenolate mofetil], cyclophosphamide, no immunosuppression), although there may be a signal in favour of immunosuppression for early dcSSc,” Ariane L. Herrick, MD, professor of rheumatology at the University of Manchester in the United Kingdom, and colleagues wrote in their study. “Although skin score improved in all treatment groups, this was least in the no immunosuppressant category, who also had the highest mortality,” they added.

Dr Herrick and colleagues said the design of ESOS differed from a typical observational study. “[I]ts standardised protocols emulated the conditions of a clinical trial, and although not randomised, patients were enrolled into four homogenous treatment arms with well-defined interventions and a systematic record of protocol changes and exits,” they wrote.

The researchers performed a prospective, observational study of 326 patients with early dcSSc from 50 centers who received methotrexate (oral or subcutaneous, 20-25 mg per week), cyclophosphamide (intravenous 500 mg/m² for 6-12 months or oral 1-2 kg/day for 12 months), MMF twice daily (500 mg), or no immunosuppressant. Patients were included if they experienced skin thickening within 3 years of beginning the study. Of the patients included, 65 patients received methotrexate, 87 patients received cyclophosphamide, 118 patients received MMF, and 56 patients received no immunosuppressant.

The researchers noted that the group not using immunosuppressants was not a control group. “Patients in this group had a longer disease duration than the other three groups and were more likely to have renal involvement,” Dr Herrick and colleagues observed.

A total of 84.7% of patients completed 12-month follow-up (n = 276), and 71.7% of patients completed 24-month follow-up (n = 234). At 12 months, all patients showed statistically significant reductions in modified Rodnan skin scores in the methotrexate (−4.0 units; 95% CI, −5.2 to −2.7), MMF (−4.1; 95% CI, −5.3 to −2.9), cyclophosphamide (−3.3; 95% CI, −4.9 to −1.7), and no immunosuppressant (−2.2; 95% CI, −4.0 to −0.3) groups (between-group differences, P =.0346).

Although Dr Herrick and colleagues found no statistically significant differences in survival among the groups, the group not using immunosuppressants had an 84.0% survival rate at 24 months.

Summary and Clinical Applicability

The researchers noted that immunosuppressants were indicated for early dcSSc, but more research is needed about better treatments after 12 months, where there was a modest benefit of using immunosuppressants.

“The message for clinicians is that there is a weak signal to support using immunosuppressants for early dcSSc (and in particular cyclophosphamide for patients with pulmonary fibrosis),” Dr Herrick and colleagues concluded. “However, it is clear that there remains a pressing need for the development of more effective and targeted treatments.”

Study Limitations

• Researchers noted that the observational nature of the study limited their ability to completely separate patients’ initial characteristics with the outcome for their treatment group.

Disclosures

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