A large study following patients in the early stages of diffuse cutaneous scleroderma showed that immunosuppressants offered only a negligible benefit for those who took them, compared to those who didn’t.
Since immunosuppressants produced numerically larger reductions in skin symptoms, the findings may support patients using such drugs from the onset of their disease. But since differences between treated and untreated patients were not statistically significant, the study may also point to the need for better treatments.
The study, “Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS),“ appeared in the journal Annals of the Rheumatic Diseases.
The rarity of diffuse cutaneous scleroderma makes it difficult to organize clinical trials to evaluate and compare different treatment options. Researchers at Britain’s University of Manchester undertook such an evaluation by instead conducting what is known as an observational study (NCT02339441, ESOS).
The study recruited 326 patients from 50 clinics across Europe. Physicians could choose to treat patients with one of four approaches: methotrexate, CellCept (mycophenolate mofetil), Cytoxan (cyclophosphamide), or no immunosuppressant.
Patients were assessed every third month, with a final examination after two years. Of the total, 65 patients were prescribed methotrexate, 118 received CellCept, 87 Cytoxan, and 56 were given no immunosuppressants at all. However, a number of patients used other medications, with nearly one-third taking corticosteroids.
Many switched treatments during the study, with 18.4 percent switching once, 3.7 percent twice, and 0.3 percent (one patient) changing treatments three times.
The study’s main focus was to measure changes in the modified Rodnan skin score. At the beginning, the median score for the entire group was 21, and the treatment groups did not differ in how much they were affected.
Since the groups differed in other aspects, including duration of skin thickening and the presence of various organ involvement, researchers included these features in the analysis.
The skin score had dropped by 2.9 units after one year, and by 6.7 units after two years. Although the study’s main endpoint was two years, researchers reported their findings in the treatment groups as an annual average.
This analysis showed that all four groups saw statistically significant reductions in skin score. Improvement was greatest for patients treated with CellCept; their scores improved by a median of 4.1 points. Methotrexate users improved by 4.0 points, Cytoxan users by 3.3 points, and the no-immunosuppressant group by 2.2 points.
Nevertheless, statistically significant and clinically meaningful results are not always the same thing. According to an earlier analysis of minimal important differences in the modified Rodnan skin score, improvements of less than 3.2 points are not clinically relevant.
Likewise, although the numerical improvement was nearly twice as large in CellCept-treated patients compared to those without immunosuppression, the differences between the groups were not statistically significant.
The study also examined if different treatments resulted in varying survival rates. Again, no statistically significant differences emerged, although those without treatment had the poorest predicted survival rate at 84 percent. At the other extreme were methotrexate users, with a predicted two-year survival rate of 94.1 percent.
“The message for clinicians is that there is a weak signal to support using immunosuppressants for early dcSSc [difuse cutaneous systemic sclerosis],” the team concluded. “However, it is clear that there remains a pressing need for the development of more effective and targeted treatments.”