Background EULAR recommendations for the treatment of Systemic Sclerosis (SSc) were updated in 2017, informed by a systematic literature review (SLR) completed in 2014. Given the high number of SSc-related clinical manifestations and therapy-related publications in the last decade, a new SLR providing the most up-to-date literature to underpin contemporary recommendations for the management of SSc was required.

Objectives The aim of this SLR was to provide a critical review of the updated evidence to address the questions prioritized by an international task force.

Methods 67 clinical questions addressing 30 interventions were explored. Three categories of questions were defined: Type I Questions that were unchanged as compared to the previous set of recommendations; Type II questions exploring the efficacy/effectiveness of an intervention already mentioned in the previous recommendations but with new outcome(s); Type III questions including interventions not mentioned in the previous recommendations. Each interventions was considered independently, with 30 SLRs for 30 interventions (including several outcomes/clinical questions), and 1 dedicated SLR (with several interventions) for calcinosis (31 searches in total). Search strategies were defined with a librarian and a methodologist. Questions were divided among 5 reviewers and three databases were screened (Embase, pubmed and Cochrane Library). Full texts eligible for data extraction were selected according to the PICOS strategy. Data extraction was performed using a pre-defined template. Quality appraisal was performed using the JADAD scale. 10% of all articles were assessed by a second reviewer ensuring consistency and reliability of data extraction. The level of evidence and grade of recommendations were defined according to the CEBM criteria.

Results For the first round of SLR, search periods were defined as follows in all three databases: new abstracts released from October 1^st 2014 to March 31^st 2022 for type I & type II questions and from database inception to march 31^st 2022 for type III questions. 14490 abstracts were retrieved from the databases on march 31^st 2022 and 18 abstracts were selected manually from march 31^st 2022 to October 11th 2022 (date of the nominal group technique (NGT) exercise). 483 new full-texts were evaluated and 172 new articles were included. 187 articles from the SLR for the 2017 recommendations were included as well. For each questions and sub-questions, the reviewers provided a summary of the current knowledge, specifying the level of evidence (1 to 5) and the level of recommendations (A to D). Each summary was reviewed by task force leaders and presented during the NGT meeting to inform discussion and voting on the new recommendations. The majority of the questions covered by this SLR explored new interventions that had not been explored in previous recommendations (40% of type III questions) or with new outcomes (26% of type II questions). New interventions included targeted therapies such as abatacept, JAK inhibitors or nintedanib, and updated questions incorporated the results from key game-changing RCTs including trials on tocilizumab, mycophenolate or rituximab in SSc-interstitial lung disease.

Conclusion This SLR provides the highest level of evidence to address questions prioritized in the 2023 update of EULAR recommendations for the treatment of SSc, providing an unprecedented comprehensive overview of recent knowledge on SSc treatments and participating in defining the future research agenda for SSc management.

Acknowledgements The authors thank all the members of the EUSTAR SSc recommendations update task force.

Disclosure of Interests Alain LESCOAT: None declared, Eugenia Bertoldo: None declared, Jelena Colic: None declared, Tânia Santiago: None declared, Yossra A. Suliman: None declared, Jenny Emmel: None declared, Philip G Conaghan: None declared, Yannick Allanore Consultant of: AbbVie, AstraZeneca, Bayer, Boehringer-Ingelheim, Mylan, Janssen, Medsenic, Prometheus, Sanofi, Roche, Grant/research support from: Alpine Immunosciences, Medsenic, OSE Immunotherapeutics, Francesco Del Galdo Speakers bureau: Boehringer Ingelheim, Jannsen, AstraZeneca, Consultant of: AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Jannsen, Mitsubishi-Tanabe, Grant/research support from: Abbvie, AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Kymab, Jannsen, Mitsubishi-Tanabe.

Keywords: Systemic sclerosis, Systematic review, Targeted synthetic drugs

DOI: 10.1136/annrheumdis-2023-eular.4742