Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug A Randomized Clinical Trial

作者：Gottenberg Jacques Eric^*; Brocq Olivier; Perdriger Aleth; Lassoued Slim; Berthelot Jean Marie; Wendling Daniel; Euller Ziegler Liana; Soubrier Martin; Richez Christophe; Fautrel Bruno; Constantin Arnaud L; Mariette Xavier; Morel Jacques; Gilson Melanie; Cormier Gregoire; Salmon Jean Hugues; Rist Stephanie; Liote Frederic; Marotte Hubert; Bonnet Christine; Marcelli Christian; Sellam Jeremie; Meyer Olivier; Solau Gervais Elisabeth; Guis Sandrine; Ziza Jean Marc

来源：Journal of the American Medical Association, 2016, 316(11): 1172-1180.

DOI：10.1001/jama.2016.13512

IMPORTANCE One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor alpha (TNF-alpha) inhibitors; little guidance on choosing the next treatment exists.
OBJECTIVE To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor.
DESIGN, SETTING, AND PARTICIPANTS A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] >= 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013.
INTERVENTIONS Patients were randomly assigned (1: 1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician.
MAIN OUTCOMES AND MEASURES The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 <= 3.2), remission (DAS28 <2.6); serious adverse events; and serious infections.
RESULTS Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003).
CONCLUSIONS AND RELEVANCE Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication.

• 出版日期2016-9-20