AB0482\u2005PHARMACOLOGICAL TREATMENT OF ENTHESITIS - A SYSTEMATIC REVIEW ON THE EFFICACY OF THE AVAILABLE OPTIONS

Abstract

Enthesitis is a recognized as a hallmark of spondyloarthrtis (SpA), including psoriatic arthritis (PsA). However, it is an underestimated disease domain in both in clinical trials and clinical practice (1).This systematic literature review (SLR) assessed the efficacy of the available pharmacological options for enthesitis.A SLR was conducted following the PRISMA reporting guidelines. Studies were sourced from PubMed and Embase databases, using the MeSH terms: enthesitis, entheses, treatment, spondylarthritis, ankylosing spondylitis and psoriatic arthritis. The search was limited to articles in English published between January 2000 and July 2020. Two independent reviewers screened the titles and abstracts.A total of 65 articles matched the research criteria. The included populations, the time to assessment of the primary endpoint and the chosen outcome for assessment of enthesitis was heterogeneous across studies. There were no studies assessing the effect of non-steroidal anti-inflammatory drugs, glucocorticoids, or csDMARDs. In PsA, all TNFis showed superiority in monotherapy against placebo (PBO). However, when combined with methotrexate (MTX), only some TNFi showed superiority against MTX monotherapy. In SpA, there was conflicting evidence regarding the efficacy of TNFi in enthesitis. Regarding IL23i in PsA, Ustekinumab was superior to PBO, and to TNFis. Guselkumab was superior to PBO when given every 4 weeks. Regarding IL7i, Secukinumab (SEC) was superior to PBO, only for some dosing schemes. Ixekizumab (IXE) was superior to PBO for the treatment of enthesitis only in TNF-naïve patients. Studies comparing SEC and IXE to ADA, showed no difference. There was no reported data on IL17i for enthesitis in SpA. In PsA, Tofacitinib was superior to PBO in naïve patients, and Tofacitinib 10mg was superior to PBO in bioexperienced patients. Apresmilast 30mg showed superiority to PBO for enthesitis. All finding are summarized on Table 1.Table 1.Findings of the systematic literature review on treatment options for enthesitisDiseaseTested drug vs ReferenceSuperiority of the treatment arm against reference arm (p<0.05)ReferencePsATNFi vs PBOYESNCT00051623 (IFX)NCT00265096 (GOL)NCT01087788 (CZP)TNFi+MTX vs PBO+MTX(PBO+ETN one study) vs PBO+MTXNONCT00367237 (IFX)NCT02065713 (GOL)NCT02376790 (ETN)UST vs PBOYESNCT01009086NCT01077362UST vs TNFiYESEudraCT 2017-003799-29 βGUS q4w vs PBOGUS q8w vs PBOYESNONCT03162796NCT03158285SEC (pooled dose) vs PBOYESNCT01392326NCT01752634SEC 300mg vs PBOSEC 150mg vs PBOYESNONCT01989468SEC 300mg with loading vs PBOSEC 150mg with loading vs PBOSEC 150mg no loading vs PBOYESYESNONCT02404350IXE vs PBOADA vs PBOYESNOPsA BionaiveNCT01695239IXE vs PBONOPsA BioexperiencedNCT02349295IL17i (SEC/ ADA) vs TNFiNONCT02745080 (SEC)NCT03151551 (ADA) βAPR 20mg vs PBOAPR 30mg vs PBONOYESNCT01172938TOF 5mg vs PBOTOF 10mg vs PBOADA 40mg vs PBONOYESNONCT01877668 (TNFi-naive)TOF vs PBONONCT01882439 (TNFi-failure)SpAETN vs SSZYES (imaging)/ NO (clinical)axSpANCT00844142ETN vs PBOYES for nr-axSpANCT01258738ADA vs PBOYES for r-axSpANO for nr-axSpAYES for perSpANCT00195819NCT00939003NCT01064856GOL IV vs PBOYES for r-axSpANCT02186873GOL 100mg vs PBOGOL 50mg vs PBOYESNOFor r-axSpANCT00265083GOL vs PBOYES nr-axSpANCT01453725β-Open-label; PsA: Psoriatic arthritis; r-axSpA: Radiologic axial spondylarthritis; nr-axialSpA: non radiological axial spondylarthritis; PBO: Placebo; TNFi: Tumor necrosis factor inhibitors; ETN: Etanercept; IFX: Infliximab; ADA: Adalimumab; GOL: Golimumab; UST: Ustekinumab; CZP: Certolizmab; GUS: Guselkumab; SEC: Secukinumab; IXE: Ixekizumab; APR: Apremilast; TOF: Tofacitinib; MTX - MethotrexateThis SLR emphasizes the current heterogeneity in the assessment and report of enthesitis. There is still an unmet need for further studies to improve our understanding about enthesopathy.[1]Schett G. et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017;13(12):731-41.Rita Pinheiro Torres: None declared., Santiago Rodrigues-Manica Speakers bureau: Novartis, Janssen and MSD, Fernando Pimentel dos Santos: None declared.