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Muscle involvement in systemic sclerosis: points to consider in clinical trials


Walker, Ulrich A; Clements, Philip J; Allanore, Yannick; Distler, Oliver; Oddis, Chester V; Khanna, Dinesh; Furst, Daniel E (2017). Muscle involvement in systemic sclerosis: points to consider in clinical trials. Rheumatology, 56(Suppl 5):v38-v44.

Abstract

SSc is clinically and pathogenetically heterogeneous. Consensus standards for trial design and outcome measures are needed. International experts experienced in SSc clinical trial design and a researcher experienced in systematic literature review screened the PubMed and Cochrane Central Register of Controlled Trials in order to develop points to consider when planning a clinical trial for muscle involvement in SSc. The experts conclude that SSc-associated muscle involvement is heterogeneous and lacks a universally accepted gold-standard for measuring therapeutic response. Although outcome studies are currently limited by the inability to clearly distinguish active, reversible muscle inflammation from irreversible muscle damage and extramuscular organ involvement, strong consideration should be given to enrolling patients with a myopathy that features several elements of likely reversibility such as muscle weakness, biopsy-proven active inflammation, an MRI indicating muscle inflammation and a baseline serum creatinine kinase above three times the upper limit of normal to prevent floor effect. Randomized controlled trials are preferred, with a duration of at least 24 weeks. Outcome measures should include a combination of elements that are likely to be reversible, such as muscle weakness, biopsy-proven active inflammation, creatinine kinase/aldolase and a quality of life questionnaire. The individual measurements might require a short pre-study for further validation. A biological sample repository is recommended.

Abstract

SSc is clinically and pathogenetically heterogeneous. Consensus standards for trial design and outcome measures are needed. International experts experienced in SSc clinical trial design and a researcher experienced in systematic literature review screened the PubMed and Cochrane Central Register of Controlled Trials in order to develop points to consider when planning a clinical trial for muscle involvement in SSc. The experts conclude that SSc-associated muscle involvement is heterogeneous and lacks a universally accepted gold-standard for measuring therapeutic response. Although outcome studies are currently limited by the inability to clearly distinguish active, reversible muscle inflammation from irreversible muscle damage and extramuscular organ involvement, strong consideration should be given to enrolling patients with a myopathy that features several elements of likely reversibility such as muscle weakness, biopsy-proven active inflammation, an MRI indicating muscle inflammation and a baseline serum creatinine kinase above three times the upper limit of normal to prevent floor effect. Randomized controlled trials are preferred, with a duration of at least 24 weeks. Outcome measures should include a combination of elements that are likely to be reversible, such as muscle weakness, biopsy-proven active inflammation, creatinine kinase/aldolase and a quality of life questionnaire. The individual measurements might require a short pre-study for further validation. A biological sample repository is recommended.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:autoantibodies, idiopathic inflammatory myopathy, muscle biopsy, muscle enzymes, muscle imaging, muscle strength, myositis, scleroderma, treatment outcome, trial design
Date:1 September 2017
Deposited On:24 Oct 2017 14:08
Last Modified:19 Feb 2018 09:00
Publisher:Oxford University Press
ISSN:1462-0324
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/rheumatology/kex196
PubMed ID:28992167

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