Fig. 3: Clinical composite outcomes and disease activity.

a, The percentage of patients who had an ACR20 response at 3 months, the primary efficacy end point of this study. Patients with missing data or who received rescue treatment were imputed as nonresponders. Stimulation, n = 122; sham, n = 120. b, The percentage of patients who had an ACR20 response through 12 months. Within double-blind period; stimulation, n = 122; sham, n = 120. At 6, 9 and 12 months, n = 97, 89, 77 in arm 1, respectively, and n = 98, 87, 81 in arm 2, respectively. c, The percentage of patients who had a DAS28-CRP good or moderate response according to the EULAR criteria. At 3, 6, 9 and 12 months, n = 118, 95, 85, 75 in arm 1, respectively, and n = 117, 98, 82, 79 in arm 2, respectively. d, The percentage of patients who had achieved LDA or remission by DAS28-CRP criteria (score < 3.2). At 3, 6, 9 and 12 months, n = 118, 95, 85, 75 in arm 1, respectively, and n = 117, 98, 82, 79 in arm 2, respectively. All data are presented as the percentage of each group with s.e. Formal statistical analyses were only performed at the 3-month study visit (double-blind) with the Cochran–Mantel–Haenszel (CMH) test using stratification factors based on prespecified criteria (prior inadequate or lost response to a tsDMARD, prior inadequate or lost response to ≥4 biological DMARDs with ≥2 mechanisms of action and RA disease severity defined as either <4 TJC28 or <4 SJC28 at day 0), at a one-sided significance level of 0.025. P = 0.0209, 95% CI = 0.6–23.1 (a,b). P = 0.0048, 95% CI = 7.3–31.7 (c). P = 0.0154, 95% CI = 1.2–21.6 (d). After 3 months (open-label stimulation), patients were permitted to augment therapy with adjunctive drugs without restriction. Data presented at 6, 9 and 12 months in b–d include all patients completing the visit who had not used augmented therapy. Percent of patients with augmented therapy—6 months = 17.8%, 9 months = 24.8%, 12 months = 32.2%. BL, baseline. *P < 0.025, **P < 0.01.