Safety and effectiveness of mycophenolate in systemic sclerosis. A systematic review.
BACKGROUND
Mycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use in systemic sclerosis (SSc) since gastrointestinal involvement is common. The objective of this study is to evaluate gastrointestinal adverse events of mycophenolate in SSc. Secondarily we evaluated other adverse events, and the effectiveness of mycophenolate in skin and lung disease.


METHODS
A literature search of Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL (inception-2013) was performed. Studies reporting use of mycophenolate in SSc patients, adverse events, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusing capacity of carbon monoxide (DLCO) were included. The primary outcome was gastrointestinal events occurring after the initiation of mycophenolate. Secondary safety outcomes included myelosuppression, infection, malignancy, and death after the initiation of mycophenolate.


RESULTS
617 citations were identified and 21 studies were included. 487 patients were exposed to mycophenolate. The mean disease duration ranged between 0.8-14.1 years. There were 18 deaths and 90 non-lethal adverse events. The non-lethal adverse events included 43 (47.7%) gastrointestinal events, 34 (26%) infections, 6 (5%) cytopenias and 2 (2%) malignancies. The most common gastrointestinal events included diarrhea (n=18 (14%)), nausea (n=12 (9%)), and abdominal pain (n=3 (2%)). The rate of discontinuation ranged between 8%-40%. Seven observational studies reported improvement or stabilization in FVC, and 5 studies report stabilization or improvement in MRSS.


CONCLUSIONS
Mycophenolate-associated gastrointestinal adverse events are common in SSc, but not severe enough to preclude its use. Observational data suggests mycophenolate may be effective in improving or stabilizing interstitial lung disease, and skin involvement.
Toronto Scleroderma Program, Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Rheumatology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia.
Mohammed A
MA
Omair
Toronto Scleroderma Program, Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Mount Sinai Hospital, Toronto, Ontario, Canada.
Abdulaziz
A
Alahmadi
Toronto Scleroderma Program, Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Mount Sinai Hospital, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
Sindhu R
SR
Johnson
D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012867:Skin / Q000473:pathology; D016896:Treatment Outcome
D009173:Mycophenolic Acid