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Rheumatoid arthritis treated with 6-months of first-line biologic or biosimilar therapy: an updated systematic review and network meta-analysis


Simpson EL1, Ren S1, Hock ES1, Stevens JW1, Binard A2, Pers YM3, Archer R4, Paisley S4, Stevenson MD4, Herpin C5, Ghabri S5. Int J Technol Assess Health Care. 2019 Feb 6:1-9. doi: 10.1017/S0266462318003628. [Epub ahead of print]

Author Information

1 School of Health and Related Research (ScHARR),University of Sheffield,United Kingdom.

2 Department of Rheumatology,CHU de la Cavale-Blanche,Brest,France.

3 Clinical Immunology and Osteoarticular Diseases Therapeutic Unit,Lapeyronie University Hospital,Montpellier,France.

4 School of Health and Related Research (ScHARR), University of Sheffield,United Kingdom.

5 Department of Economic and Public Health Evaluation,French National Authority for Health (HAS), Saint-Denis La Plaine,France.



The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.


Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.


Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.


In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.