Advances in Scleroderma
Lorinda Chung, MD, MS, director of the Scleroderma Center and co-director of the Multidisciplinary Rheumatologic Dermatology Clinic at Stanford University School of Medicine, Palo Alto, Calif., spoke about advances in scleroderma.
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Explore This IssueApril 2020
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A key element of monitoring cutaneous disease activity in scleroderma relies on the use of the modified Rodnan Skin Score (mRSS), which is a measure of skin thickness on a scale of 0–3 (higher score representing thicker skin) at 17 body sites, with a possible total score of 0–51. Dr. Chung noted that several risk factors have been identified as predictors of progression of cutaneous disease in scleroderma, and these include low baseline mRSS, presence of synovitis at baseline and anti-RNA polymerase III antibody positivity. However, the mRSS is sometimes insufficient on its own to enable overall disease progression to be tracked in patients with scleroderma and may not be the most comprehensive way to evaluate efficacy of treatments in clinical trials.
Dr. Chung noted that, in 2016, the ACR developed the Composite Response Index in Systemic Sclerosis (CRISS) to better address these needs.3 The CRISS uses a two-step process that begins with the question: Has the patient demonstrated worsening cardiac, pulmonary or renal manifestations of scleroderma?
If the answer is yes, specifically with regard to new scleroderma renal crisis, a decline of 15% or more in forced vital capacity (FVC) in patients with interstitial lung disease, new pulmonary hypertension on right heart catheterization or new left ejection fraction of less than 45%, then the patient is noted not to have improved on whichever treatment they are using.
If the answer is no, then the mRSS, percent-predicted FVC, patient and physician global assessments, and the Health Assessment Questionnaire Disability Index (HAQ-DI) are used to calculated a CRISS score to indicate the likelihood the patient has improved on treatment.
Dr. Chung explained that use of the CRISS score in clinical trials may hold a great deal of potential to better evaluate if treatments are efficacious in patients with scleroderma.
Another important clinical study in recent years was the Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, in which the authors compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma.4 The primary endpoint in this study was a global rank composite score that included death, event-free (respiratory, renal or cardiac failure) survival, FVC, HAQ-DI and mRSS. In an intention-to-treat analysis, 67% of pairwise comparisons using the global score favored transplantation over cyclophosphamide at 54 months.
It has been noted that the treatment-related mortality in the transplantation group was 6% at 72 months, compared with 0% in the cyclophosphamide group, and that the composite score used in this study has not been widely used in other studies. Dr. Chung explained that some patients with severe cutaneous disease who have not done well on methotrexate, mycophenolate mofetil or cyclophosphamide may be candidates for myeloablative autologous hematopoietic stem cell transplantation.
Despite only brief mention, it is also important to note that nintedanib, a tyrosine kinase inhibitor, is the first medication\ approved by the U.S. Food & Drug Administration for the treatment of interstitial lung disease associated with scleroderma.