Biologic therapy for systemic sclerosis: a systematic review.
OBJECTIVE
Biologic agents are increasingly used in the rheumatic diseases. Their role in patients with systemic sclerosis (SSc) is uncertain. Our aim was to evaluate the effectiveness and safety of biologic agents in SSc. We review the evidence for the use of biologic agents to improve inflammatory arthritis, disability, and skin score, and we review adverse effects with biologic agents in patients with SSc.


METHODS
A systematic literature review was performed to identify studies evaluating the use of biologic agents in SSc. Medline, Embase, CINAHL, and Cochrane Database of Systematic Reviews were searched. A standardized abstraction form was used to extract biologic agent, study design, sample size, treatment effect, and adverse effects.


RESULTS
A total of 23 studies from 1413 citations were evaluated. Three studies evaluated infliximab, 3 evaluated etanercept, 3 evaluated antithymocyte globulin, 3 evaluated imatinib, 6 evaluated rituximab, and 1 study each evaluated interferon-γ (IFN-γ), IFN-α, relaxin, delipidated, deglycolipidated Mycobacterium vaccae, human anti-transforming growth factor ß1 antibody, and oral type I collagen. Studies of etanercept and infliximab suggest improvements in inflammatory arthritis and Health Assessment Questionnaire Disability Index (HAQ-DI). None of the other biologic agents demonstrated reproducible, statistically significant improvements in joint count, HAQ-DI, or skin score.


CONCLUSIONS
Anti-tumor necrosis factor-α agents may improve inflammatory arthritis and disability in SSc. The effect on skin score is uncertain. Adequately powered trials are needed to evaluate efficacy, and longitudinal studies are needed to evaluate longterm safety of these agents in SSc.
Division of Rheumatology, Ground Floor, East Wing, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
Veerapong
V
Phumethum
Shahin
S
Jamal
Sindhu R
SR
Johnson
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001549:Benzamides; D001691:Biological Therapy / Q000379:methods*; D000068800:Etanercept; D006801:Humans; D000068877:Imatinib Mesylate; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D016898:Interferon-alpha / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D001549:Benzamides; D007074:Immunoglobulin G; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068877:Imatinib Mesylate; D000069285:Infliximab; D000068800:Etanercept