To assess current evidence of effectiveness of sequential lines of biologic and targeted small molecule drugs for psoriasis beyond first line. A systematic search of the literature (Medline, Embase and bibliographic) was undertaken in October and December 2022 to find all studies assessing effectiveness of biologics and targeted small molecules when used beyond first-line in adults with psoriasis (PROSPERO CRD42022365298). Data extraction and a bias assessment (Risk Of Bias In Non-randomized Studies-of Interventions/Cochrane RoB2) were undertaken for all included studies. A random effects proportional meta-analysis was undertaken for PASI75/90/100 at 12-16 weeks for each line of treatment (1st to 4th). Of 2666 abstracts identified, a full text review was undertaken of 177 studies; 20 manuscripts met eligibility criteria. Twenty studies were included in the analysis: 19 observational studies and one sub analysis of a RCT; n = 6495 (average age 49.7 years, female 35.1%). Eleven studies assessed second line biologic, nine assessed third + line. A meta-analysis of PASI75 at 12-16 weeks found pooled effect percentage achieving PASI75 of 61%, 56%, 79% and 61% in 1st, 2nd, 3rd and 4th line biologics respectively. Meta-analyses of PASI90/100 also found no evidence of diminished effectiveness with sequential lines (PASI90 46.1%, 39.9%, 55.8% and 33.7% and PASI100 36.7%, 30.3%, 46.7% and 30.4% in 1st to 4th line respectively). Available evidence for effectiveness of biologics beyond first line in psoriasis is predominantly observational, at high risk of bias and of low quality. There is very limited data for effectiveness beyond second line. Evidence indicates that biologics can be effective to fourth-line.
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