eprintid: 10178243 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/17/82/43 datestamp: 2023-10-06 11:56:16 lastmod: 2024-11-02 07:10:06 status_changed: 2023-10-06 11:56:16 type: article metadata_visibility: show sword_depositor: 699 creators_name: Herrick, Ariane L creators_name: Denton, Christopher P title: Enrichment strategies for clinical trials targeting skin fibrosis and interstitial lung disease in systemic sclerosis ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G90 note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: PURPOSE OF REVIEW: This review gives an update on enrichment strategies for clinical trials in patients with systemic sclerosis (SSc) in two contexts - skin fibrosis in early diffuse cutaneous disease, and SSc-related interstitial lung disease (ILD) - focusing on reports from the last 18 months. Lessons have been learnt from recent studies, making this review timely. RECENT FINDINGS: Recent trials have highlighted how patients included into trials must be carefully selected to include 'progressors', that is, those most likely to benefit from treatment, and how drug mechanism action of action will influence trial design. For skin fibrosis, current enrichment strategies are mainly on clinical grounds (including disease duration, extent of skin thickening, tendon friction rubs and anti-RNA polymerase III positivity). Gene expression signatures may play a role in the future. For ILD, current enrichment strategies (degree of lung involvement as assessed by pulmonary function and high-resolution computed tomography) may help to recruit the most informative patients, but should avoid being too stringent to be feasible or for findings to be generalizable. SUMMARY: Both skin fibrosis and ILD trials are challenging in SSc. Ongoing work on enrichment strategies should help to differentiate effective new treatments from placebo with smaller sample sizes than have been included in recent studies. date: 2023-11-01 date_type: published publisher: Ovid Technologies (Wolters Kluwer Health) official_url: http://doi.org/10.1097/BOR.0000000000000976 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2093546 doi: 10.1097/BOR.0000000000000976 medium: Print-Electronic pii: 00002281-990000000-00084 lyricists_name: Denton, Christopher lyricists_id: CPDEN87 actors_name: Denton, Christopher actors_id: CPDEN87 actors_role: owner full_text_status: public publication: Current Opinion in Rheumatology volume: 35 number: 6 pagerange: 349-355 event_location: United States issn: 1040-8711 citation: Herrick, Ariane L; Denton, Christopher P; (2023) Enrichment strategies for clinical trials targeting skin fibrosis and interstitial lung disease in systemic sclerosis. Current Opinion in Rheumatology , 35 (6) pp. 349-355. 10.1097/BOR.0000000000000976 <https://doi.org/10.1097/BOR.0000000000000976>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10178243/1/CurrOp_Skin-ILD-Herrick%20Denton-for%20UCL%20upload.pdf