Background Rare rheumatic diseases are challenging for both patients and clinicians. This problem is further propelled by the scarce number of approved treatment regimens. Therapy is often limited to immunosuppression with corticosteroids or off-label use of drugs for common rheumatic diseases.
Objectives We have recently described a set of 82 classified rare diseases in rheumatology . In this systematic review, we analysed the evidence for therapeutic regimens from randomized clinical trials of rare rheumatic diseases.
Methods For this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PUBMED and SCOPUS, up to 20th of October 2016. To validate the search strategy, we selected sentinel references.
We included randomized controlled trials regarding rare rheumatic diseases and put a focus on pharmacological treatment compared with placebo, application of two drugs, or standard therapy. The term “rare” was defined by the European Union as a condition that occurs in no more than 1 in 2,000 individuals.
Two review authors independently assessed trial quality and extracted the data. We screened the search results and included studies if they met the selection criteria. If we identified two or more trials that investigated the same rare disease and used the same assessment tools we performed a meta-analysis.
Results 135 studies were screened, of which 34 met the inclusion criteria. In total, we analysed data on 11 different orphan diseases, encompassing 2,324 participants. There was a high degree of statistical and clinical heterogeneity in these trials. Several sources of potential bias were identified in the included studies, for example, a lack of description of the blinding methods and allocation concealment, as well as the small size of the study populations. We included studies such as rituximab against cyclophosphamide in ANCA-associated vasculitis. These studies demonstrated a non-inferiority of rituximab. The meta-analysis resulted a combined odds ratio (OR) of 1.42 in favour of rituximab (95% CI). Further meta-analyses were possible for another 22 studies involving, among others, Behçet's disease, systemic sclerosis, cryopyrin-associated periodic syndromes, and giant cell arteritis. Compounds studied were immunosuppressants like corticosteroids, methotrexate and azathioprine, or biologicals such as rilonacept, infliximab, and canakinumab.
Conclusions A high degree of evidence is hampered by the limited number of study participants in each trial. On the other hand, diseases such as systemic sclerosis, ANCA-associated vasculitides, or Behçet's disease had more high quality trials available. The amount of data for most other rare disease remains unsatisfactory.
Leyens J, Stieber C, Bender TTA, Mücke M, Seidel MF. (2016) Classification of rare diseases in rheumatology demonstrates a combined prevalence double to the prevalence of ankylosing spondylitis. Ann. Rheum. Dis. 75(Suppl2): 618.
Disclosure of Interest None declared