Extended report ACR20 ACR50 ACR70 EULAR response* Clinical remission† HAQ–DI response‡ DAS28–CRP§ Baseline, mean (SD) Week 24, mean (SD) Adjusted mean (SE) change DAS28–ESR§ Baseline, mean (SD) Week 24, mean (SD) Adjusted mean (SE) change HAQ–DI§ Baseline, mean (SD) Week 24, mean (SD) Adjusted mean (SE) change FACIT–F¶ Baseline, mean (SD) Week 24, mean (SD) Adjusted mean (SE) change SF-36 physical component summary score** Baseline, mean (SD) Week 24, mean (SD) Adjusted mean (SE) change SF-36 mental component summary score** Baseline, mean (SD) Week 24, mean (SD) Adjusted mean (SE) change 64/129 (50%) 35/129 (27%) 17/129 (13%) 87/129 (67%) 13/129 (10%) 74/129 (57%) 5.83 (0.794) 4.12 (1.270) −1.77 (0.151) 6.59 (0.828) 4.84 (1.360) −1.79 (0.157) 1.7 (0.67) 1.2 (0.79) −0.53 (0.077) 25.2 (10.00) 32.0 (11.52) 7.29 (1.353) 29.9 (6.73) 35.9 (9.28) 6.69 (1.031) 38.2 (11.77) 42.2 (11.38) 4.60 (1.272) Table 2 Summary of disease-activity and quality-of-life clinical endpoints at week 24 for patients receiving ofatumumab or placebo Ofatumumab 700 mg (n=129) Placebo (n=131) OR (95% CI) Ofatumumab 700 mg (n=129) Placebo (n=131) Adjusted mean difference (95% CI) 35/131 (27%) 14/131 (11%) 3/131 (2%) 54/131 (41%) 7/131 (5%) 59/131 (45%) 5.63 (0.800) 4.98 (1.437) −0.77 (0.154) 6.41 (0.782) 5.67 (1.439) −0.80 (0.161) 1.5 (0.65) 1.3 (0.74) −0.32 (0.078) 29.5 (9.54) 30.2 (10.86) 3.55 (1.394) 31.9 (7.32) 34.8 (8.79) 4.21 (1.048) 40.1 (11.84) 40.2 (11.95) 1.57 (1.308) 2.86 (1.67 to 4.91) 3.29 (1.63 to 6.62) 6.63 (1.87 to 23.51) 3.07 (1.82 to 5.18) 2.09 (0.76 to 5.77) 1.65 (1.01 to 2.70) −1.00 (−1.29 to −0.72) −0.99 (−1.29 to −0.69) −0.22 (−0.37 to −0.07) 3.75 (1.11 to 6.39) 2.48 (0.51 to 4.45) 3.03 (0.61 to 5.46) p Value <0.001 <0.001 0.001 <0.001 0.152 0.046 p Value <0.001 <0.001 0.004 0.006 0.014 0.014 ACR20/50/70, 20%/50%/70% improvement as per American College of Rheumatology (ACR) criteria. *EULAR response of moderate or good, based on DAS28–CRP. †DAS28–CRP score less than 2.6. ‡Change from baseline HAQ–DI score of 0.22 or greater. §Negative change represents an improvement. Patient numbers assessed: placebo (n=130); ofatumumab (n=126). **Patient numbers assessed: placebo (n=117); ofatumumab (n=116). ¶Patient numbers assessed: placebo (n=111); ofatumumab (n=114). Results are reported in accordance with EULAR/ACR collaborative recommendations.33 CRP, C-reactive protein; DAS28, disease activity score based on 28 joints; EULAR, European League Against Rheumatism; ESR, erythrocyte sedimentation rate; FACIT–F, functional assessment of chronic illness therapy–fatigue; HAQ–DI, health assessment questionnaire disability index; SF-36, short-form health survey. the ACR20 response in ofatumumab and placebo groups, respectively, was 50% (56/111) versus 26% (29/113) for sero- positive patients and 44% (7/16) versus 31% (5/16) for sero- negative patients. All other secondary efﬁcacy endpoints, including EULAR response and mean change from baseline in DAS28–CRP and DAS28–ESR were signiﬁcantly improved in the ofatumumab group compared with placebo, except for clinical remission (DAS28–CRP <2.6) (table 2 and supplementary table S1, avail- able online only). The mean change from baseline in DAS28–CRP scores over the 24-week period showed sustained improvement compared with placebo from week 8 to week 24 (ﬁgure 3). Ofatumumab also provided improvements in patient-reported outcomes as shown by signiﬁcantly greater changes from base- line in HAQ–DI, FACIT–F and SF36v2 scores compared with placebo (table 2). Laboratory ﬁndings Peripheral B lymphocytes (CD19) were greatly reduced at each visit relative to baseline in the ofatumumab group: median reductions at weeks 2 (before the second infusion), 4, 12 and 24 were 95%, 96%, 96% and 94%, respectively. In the placebo 2122 group, CD19 cells increased by 3% at week 24. In the ofatu- mumab group one patient (1%) had a CD19 B-cell count equal to or greater than the lower limit of normal (0.11 GI/l) or the baseline value at week 24. No trend for a change in periph- eral CD3, CD4 or CD8 T-cell counts was observed in either group. Biomarkers and assessment of immunogenicity At week 24, the median change from baseline in absolute bio- marker levels for ofatumumab and placebo, respectively, were: −4.0 versus −0.4 ng/l for IL-6; −53.5 versus −10.9 mg/ml for serum amyloid A; −138 versus 0 units for anti-CCP; −6.3 versus 0.0 units for RF–IgM; −4.8 versus 0.0 units for RF–IgG and −3.0 versus 0.0 units for RF–IgA. At week 24, the median change from baseline in immunoglobulin levels for ofatumumab and placebo, respectively, were: −1.30 versus −0.60 g/l for IgG; −0.30 versus −0.02 g/l for IgM and −0.23 versus −0.09 g/l for IgA. A small number of patients on ofatumumab or placebo had immunoglobulins equal to or less than the lower limit of nor- mal during the study (IgM 6 vs 4; IgG 3 vs 1; IgA, no patients, respectively). No patients treated with ofatumumab developed detectable anti-ofatumumab antibodies at week 24. Ann Rheum Dis 2011;70:2119–2125. doi:10.1136/ard.2011.151522