AB0482 PHARMACOLOGICAL TREATMENT OF ENTHESITIS - A SYSTEMATIC REVIEW ON THE EFFICACY OF THE AVAILABLE OPTIONS
Authors: R. Pinheiro Torres, S. Rodrigues-Manica, F. Pimentel Dos Santos
Journal: Annals of the Rheumatic Diseases (2021)

Background: 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). Objectives: This systematic literature review (SLR) assessed the efficacy of the available pharmacological options for enthesitis. Methods: 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. Results: 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 enthesitis Disease Tested drug vs Reference Superiority of the treatment arm against reference arm (p&lt;0.05 ) Reference PsA TNFi vs PBO YES NCT00051623 (IFX) NCT00265096 (GOL) NCT01087788 (CZP) TNFi+MTX vs PBO+MTX (PBO+ETN one study) vs PBO+MTX NO NCT00367237 (IFX) NCT02065713 (GOL) NCT02376790 (ETN) UST vs PBO YES NCT01009086 NCT01077362 UST vs TNFi YES EudraCT 2017-003799-29 β GUS q4w vs PBO GUS q8w vs PBO YES NO NCT03162796 NCT03158285 SEC (pooled dose) vs PBO YES NCT01392326 NCT01752634 SEC 300mg vs PBO SEC 150mg vs PBO YES NO NCT01989468 SEC 300mg with loading vs PBO SEC 150mg with loading vs PBO SEC 150mg no loading vs PBO YES YES NO NCT02404350 IXE vs PBO ADA vs PBO YES NO PsA Bionaive NCT01695239 IXE vs PBO NO PsA Bioexperienced NCT02349295 IL17i (SEC/ ADA) vs TNFi NO NCT02745080 (SEC) NCT03151551 (ADA) β APR 20mg vs PBO APR 30mg vs PBO NO YES NCT01172938 TOF 5mg vs PBO TOF 10mg vs PBO ADA 40mg vs PBO NO YES NO NCT01877668 (TNFi-naive) TOF vs PBO NO NCT01882439 (TNFi-failure) SpA ETN vs SSZ YES (imaging)/ NO (clinical) axSpA NCT00844142 ETN vs PBO YES for nr-axSpA NCT01258738 ADA vs PBO YES for r-axSpA NO for nr-axSpA YES for perSpA NCT00195819 NCT00939003 NCT01064856 GOL IV vs PBO YES for r-axSpA NCT02186873 GOL 100mg vs PBO GOL 50mg vs PBO YES NO For r-axSpA NCT00265083 GOL vs PBO YES nr-axSpA NCT01453725 β-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 - Methotrexate Conclusion: This 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. References: [1]Schett G. et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017;13(12):731-41. Disclosure of Interests: Rita Pinheiro Torres: None declared., Santiago Rodrigues-Manica Speakers bureau: Novartis, Janssen and MSD, Fernando Pimentel dos Santos: None declared.