Peripheral manifestations in spondyloarthritis: a systematic literature review on their assessment and the effect of biological/targeted synthetic DMARDs

Objectives Peripheral manifestations (peripheral arthritis/enthesitis/dactylitis) are frequent in axial spondyloarthritis (axSpA) yet, understudied. We (i) evaluated the assessment/reporting of peripheral manifestations in trials of biological or targeted synthetic DMARDs (b/tsDMARDs) for axSpA and peripheral SpA (pSpA), and (ii) synthesized the efficacy of b/tsDMARDs on these manifestations.Methods Systematic literature review (SLR) of controlled trials evaluating b/tsDMARDs in axSpA/pSpA (excluding psoriatic arthritis). Records were identified through previous SLRs informing ASAS-EULAR recommendations and updated searches. Outcomes included (i) frequency of assessment/reporting of peripheral arthritis/enthesitis/dactylitis and (ii) treatment efficacy of b/tsDMARDs on these peripheral manifestations [standardized mean differences (SMDs) or relative risk].Results We included 100 axSpA and four pSpA trials. In axSpA, peripheral arthritis was assessed in 54%, enthesitis in 64% and dactylitis in only 10% of studies. When assessed, results were reported in 69%, 72% and 10% of studies, respectively, and often in all patients (instead of those affected at baseline). Most frequently used instruments were 44-joint count for peripheral arthritis (48%), Maastricht Ankylosing Spondylitis Enthesitis Score for enthesitis (88%) and digit count for dactylitis (40%). Composite indices like DAS were not used. SMDs (range 0.26 to -1.18) indicated mainly small-to-moderate b/tsDMARD effects, typically higher in patients with baseline peripheral involvement. In pSpA, peripheral manifestations were always assessed/reported, with generally moderate effects (SMD range -0.10 to -1.22).Conclusion Peripheral manifestations are inconsistently assessed and reported in axSpA trials. While b/tsDMARDs have small-to-moderate effects on peripheral manifestations, these may be underestimated due to not being assessed in the population affected at baseline.