Sat0288 a Systematic Review of Systemic Sclerosis Clinical Trials Since 2005. Lack of Early Disease Targeting, Confusion Related to Disease Duration Definition and Low Level of Incorporation of the New Classification Criteria

Abstract

BackgroundIt is still unknown whether treatment in very early systemic sclerosis (SSc) can affect long term outcomes.ObjectivesTo systematically review clinical trials in SSc during the last 14 years aiming at answering the following questions: 1) how many clinical trials in SSc have targeted early disease and whether treatment of patients with early disease leads to better clinical outcomes, 2) how is disease duration defined in SSc clinical trials and whether data on duration since Raynaud’s onset are provided and 3) whether the new 2013 ACR/EULAR SSc criteria have been incorporated in clinical trials throughout the last 5 years.MethodsA search in published studies indexed in MEDLINE was performed from Jan-2005 to Dec-2018. The Clinical Trial filter was activated and the terms “systemic sclerosis treatment” used. Studies were included if they evaluated adult patients with systemic sclerosis, concerned systemic treatments, presented data for clinical endpoints assessing fibrosis and were prospective in design.ResultsSeventy-three studies with a total number of 3078 patients met the inclusion criteria and were subjected to data extraction. The total weighted mean disease duration (adjusted to the number of patients in each study) was 38.55 months which is more than 3 years, the usual threshold for defining early disease. Baseline total weighted mean MRSS was 21.54 indicating that most patients had full blown fibrotic disease. Only 24 studies (32.9%) recruited early (<36 months disease duration) cohorts, with only 4 studies among them concerning very early disease (<18 months disease duration). We next focused on studies that did not specifically target early disease (n=49) and explored whether disease duration associated with clinical outcomes. We identified such an analysis only in 13 studies. In 8/13 studies there was no difference regarding outcomes according to disease duration. Nevertheless, in 4/13 studies investigators reported better outcomes in patients with shorter disease duration with only one study showing the opposite. Significant heterogeneity was found regarding disease duration definition. Four separate definitions were identified: 1) “From first non-Raynaud’s symptom” (49.3%), 2) “From disease diagnosis” (11%), 3) “From skin thickening onset” (5.5%), 4) “From first symptom” (11%). The remaining studies (23.3%) presented no clear definition in their manuscript for disease duration in their cohorts. The stratification of the studies according to year of publication showed a tendency for greater consistency regarding the definition used in recent years since most studies published from 2015 and onwards use the definition “From first non-Raynaud’s symptom”. Data regarding the duration since Raynaud’s onset were available only in 9 studies (12.3%). A separate analysis of all articles published from 2014 until 2018 was performed to explore the incorporation of the new 2013 ACR/EULAR criteria. Only 6 studies (25%) incorporating the new criteria were identified.Conclusion1) The majority of patients recru...