Figure 2 ACR 20/50/70 responses at week 24 in patients receiving ofatumumab 700 mg or placebo. ACR20/50/70, 20%/50%/70% improvement as per American College of Rheumatology (ACR) criteria. Safety The overall incidence of AE was 89% and 55% in ofatumumab and placebo groups, respectively (table 3). Within the ofatu- mumab group the most commonly reported AE were rash (21%) and urticaria (12%); these events mostly occurred on the day of ﬁrst infusion (19% and 12%, respectively). The propor- tion of patients experiencing an infusion-related AE on the day of ﬁrst infusion was 68% for ofatumumab and 6% for placebo; infusion-related AE on the day of second infusion markedly declined (<1% and 0%, respectively). Most AE were of mild or moderate intensity. Severe AE were reported for 8% of patients on ofatumumab and 2% on placebo, with 5% and less than 1% occurring on the day of ﬁrst infusion. AE leading to withdrawal were 9% for ofatumumab and less than 1% for placebo. Four SAE (bacterial gastroenteritis, pneumonia, myocardial infarc- tion, ischaemic stroke) were reported for four patients (3%) in the placebo group and seven SAE (angioedema, interstitial lung disease (fatal), synovitis, pulmonary embolism, diarrhoea and pneumonia, pericardial effusion) were reported for six patients (5%) in the ofatumumab group. Two of these SAE (angioedema, pneumonia), both in the ofatumumab group, were considered by the investigator to be related to the investigational product. There was one fatal SAE of interstitial lung disease in the ofatu- mumab group, which was not considered by the investigator to be related to the investigational product but to RA worsening. AE within the system organ class of infections and infesta- tions were reported for 26% and 32% of patients on placebo and ofatumumab, respectively. None of the events was of severe intensity and none led to discontinuation of the investigational product or withdrawal from the study. One SAE of pneumonia was reported in each group and one SAE of bacterial gastroen- teritis was reported on placebo (table 3). No serious opportunistic infections and no cases of progressive multifocal leukoencephal- opathy were reported. Two neoplasms, both prostatic adenoma and both in the placebo group, were reported. DISCUSSION The results from the 24-week, placebo-controlled, double-blind phase of this trial conﬁrm the previously reported efﬁcacy of one course of intravenous ofatumumab in active RA.11 In addi- tion, this study provides further information on the efﬁcacy Ann Rheum Dis 2011;70:2119–2125. doi:10.1136/ard.2011.151522 Table 3 Safety of placebo and ofatumumab over 24 weeks (safety population) Extended report Patients with AE, n (%) Ofatumumab 700 mg (n=130) Placebo (n=130) Total patient-years of exposure Any AE Any SAE (fatal or non-fatal)* Death AE leading to discontinuation of IP or withdrawal from study Most common AE (≥5% in either group) Rash Urticaria Urinary tract infection Headache Nasopharyngitis Pruritus Throat irritation Hypersensitivity Dyspnoea Infusion reactions Any AE on day of ﬁrst infusion Infusion-related reaction† Any AE on day of second infusion Infusion-related reaction† Patients with an infection No of infections Infections/100 patient-years (95% CI) Patients with a serious infection No of infections Infections/100 patient-years (95% CI) Cardiac disorders Any Serious Vascular disorders Any Serious Neoplasms (benign or malignant) Any Serious 57 116 (89) 6 (5) 1 (<1) 12 (9) 27 (21) 16 (12) 7 (5) 6 (5) 10 (8) 10 (8) 10 (8) 8 (6) 7 (5) 92 (71) 89 (68) 4 (3) 1 (<1) 42 (32) 60 105.26 (81.86 to 135.49) 1 (<1) 1 1.75 (0.42 to 9.77) 7 (5) 1 (<1) 12 (9) 0 0 0 58 71 (55) 4 (3) 0 1 (<1) 1 (<1) 1 (<1) 9 (7) 8 (6) 3 (2) 2 (2) 1 (<1) 0 0 12 (9) 8 (6) 4 (3) 0 34 (26) 45 77.59 (58.07 to 103.82) 2 (2) 2 3.45 (1.07 to 12.46) 6 (5) 1 (<1) 8 (6) 0 2 (2) 0 *SAE were bacterial gastroenteritis, pneumonia, myocardial infarction, ischaemic stroke in the placebo group and angioedema, interstitial lung disease (fatal, unrelated to ofatumumab), synovitis, pulmonary embolism, diarrhoea and pneumonia, pericardial effusion in the ofatumumab group. †Infusion-related reactions (events likely to represent clinical signs and symptoms characteristic of ofatumumab infusion reactions in patients with RA) were identiﬁed by a safety review team before unblinding. AE, adverse event; IP, investigational product; RA, rheumatoid arthritis; SAE, serious adverse event. of ofatumumab in a well-deﬁned RA patient population with long-standing disease not controlled by standard methotrexate therapy and not previously treated with other available bio- logical DMARD therapies. Ofatumumab, at a dose of 700 mg administered twice, added to a background stable dose of meth- otrexate therapy, demonstrated a signiﬁcantly greater ACR20 response at week 24 (primary endpoint) compared with placebo. Signiﬁcantly greater improvements were observed in key sec- ondary endpoints such as ACR50, ACR70, change from baseline in both DAS28–CRP and DAS28–ESR, EULAR response, physi- cal function (HAQ–DI) and fatigue (FACIT–F). Efﬁcacy data from seronegative RA patients, for either RF or anti-CCP, as observed in the study, should be interpreted with caution because of the small sample size. Data from a number of clinical trials with rituximab in a range of RA populations seem 2123