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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
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<0.05 ) | Reference |
| PsA | TNFi vs PBO | YES | NCT00051623 (IFX)
|
| TNFi+MTX vs PBO+MTX
| NO | NCT00367237 (IFX)
|
|
| UST vs PBO | YES | NCT01009086
|
|
| UST vs TNFi | YES | EudraCT 2017-003799-29 β | |
| GUS q4w vs PBO
| YES
| NCT03162796
|
|
| SEC (pooled dose) vs PBO | YES | NCT01392326
|
|
| SEC 300mg vs PBO
| YES
| NCT01989468 | |
| SEC 300mg with loading vs PBO
| YES
| NCT02404350 | |
| IXE vs PBO
| YES
| NCT01695239 | |
| IXE vs PBO | NO
| NCT02349295 | |
| IL17i (SEC/ ADA) vs TNFi | NO | NCT02745080 (SEC)
|
|
| APR 20mg vs PBO
| NO
| NCT01172938 | |
| TOF 5mg vs PBO
| NO
| NCT01877668 (TNFi-naive) | |
| TOF vs PBO | NO | NCT01882439 (TNFi-failure) | |
| SpA | ETN vs SSZ | YES (imaging)/ NO (clinical)
| NCT00844142 |
| ETN vs PBO | YES for nr-axSpA | NCT01258738 | |
| ADA vs PBO | YES for r-axSpA
| NCT00195819
|
|
| GOL IV vs PBO | YES for r-axSpA | NCT02186873 | |
| GOL 100mg vs PBO
| YES
| 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.