Immunosuppressives Fail to Benefit Early Skin Scleroderma Save

Treatment of systemic sclerosis is difficult as there have few proven therapies capable of altering the course of the disease. Ideally, early intervention affords the optimal scenario wherein drug intervention can be proven to work.

Numerous investigators pooled their efforts in a worldwide, prospective, observational cohort study of early diffuse cutaneous systemic sclerosis (dcSSc) defined as less than 3 yrs from the onset of skin thickening. 

Open label immunosuppressive therapy was chosen by the clinicians, who selected one of four protocols: methotrexate (MTX), mycophenolate mofetil (MMF), cyclophosphamide (CTX) or ‘no immunosuppressant’. Patients were assessed every 3 months and followed for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). 

326 patients from 50 sites received MTX (65), MMF (118),  CTX (87) or no immunosuppressant (56). The dropout rate was only 15.3% at 12 mos. and 71.7% completed 24 months follow-up.

All groups had statistically significant reductions in mRSS at 12 months:

• MTX:  −4.0 (−5.2 to −2.7) units
• MMF:  −4.1 (−5.3 to −2.9)
• CTX −3.3 (−4.9 to −1.7)
• No immunosuppressant: −2.2 (−4.0 to −0.3)

There were no significant differences between groups (p=0.346). There were no statistically significant differences in survival between protocols before (p=0.389), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.

The authors concluded that the findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest.

There are several flaws with the study, including the open label design, selection of therapy by the investigator and choosing the mRSS as the primary outcome. This study proves what others have shown, that it may be a clinically important outcome but is the least discriminatory outcome over time as many patients may exhibit "regressive" cutaneous changes with time.