Preliminary Results Show Potential Of Ofatumumab In Rheumatoid Arthritis

Main Category: Arthritis / Rheumatology
Also Included In: Conferences;  Clinical Trials / Drug Trials
Article Date: 17 Jun 2007 - 0:00 PDT

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Preliminary results of an international study announced today at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain, report positively on the efficacy and safety of ofatumumab (HuMax-CD20) in the treatment of rheumatoid arthritis (RA). Ofatumumab is a fully human monoclonal antibody targeted at the CD20 molecule in the membrane of B-cells (immunological cells most commonly involved in RA).

The primary efficacy results (evaluated at 24 Weeks) from the ongoing, double-blind, randomized, parallel group, placebo-controlled multi-centre phase II trial, conducted across several international centres including the UK, France, Denmark, Poland, USA and Hungary, comprised 225 patients with active RA who had previously not responded to treatment with disease modifying antirheumatic drugs (DMARDs).

Professor Mikkel Østergaard, of Copenhagen University Hospital, Denmark, lead investigator, comments, "This first analysis of the potential of ofatumumab in rheumatoid arthritis is very encouraging indeed, showing the potential of this fully human, high-affinity antibody for the future management of patients with this debilitating condition."

The researchers gathered information on response of participants to two doses of ofatumumab 300mg, 700 mg or 1000mg or placebo administered on days 0 and 14. Results were analysed according to the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) core sets of outcome measures for RA.

At 24 weeks, a greater proportion of ofatumumab-treated patients (ITT) across all doses yielded ACR20 response rates, 300mg 41% (24/58) (p=0.002), 700mg 49% (28/57) (p<0.001) and 1000mg 46% (25/54) (p<0.001) which were significantly greater compared to 15% in those given placebo. In addition, 72% of patients in each of the three active arms experienced a moderate or good EULAR response against 40% on placebo at week 24. Rapid and sustained peripheral B-cell depletion was observed in all dose groups. All patients tested negative for human anti-human antibodies (HAHA).

80% (179/225) of the study participants were concurrently taking methotrexate at a median weekly dose of 15mg (82% (46/56) placebo; 83% (48/58) 300mg; 75% (43/57) 700mg; 78% (42/54) 1000mg). These patients obtained ACR20 responses of 42% (20/48) (p=<0.006), 56% (24/43) (p=<0.001) and 50% (21/42) (p=0.001) compared to 16% of patients receiving placebo. Between 56% and 72% of participants were receiving concomitant prednisolone at a median daily dose of 5-7.5mg (70% (39/56) of placebo arm; 72% (42/58) of 300mg; 63% (36/57) of 700mg; 56% (30/54) 1000mg). Previous exposure to biological agents was allowed except for CD20 antibodies within two years prior to inclusion. Patients were pre-medicated with paracetamol, antihistamines and glucocorticosteroids.

Of the initial 53 patients involved, two participants had a serious infusion-related reaction and one had a serious infusion-related event of bronchospasm. Consequently, the infusion rate was decreased for the succeeding 172 patients among whom only one serious infusion-related reaction and one serious infusion related event of urticaria was reported. All participants have recovered from their adverse events. The most commonly reported adverse events were rash, throat irritation and dyspnoea of grade 1-2 severity. There was no increased frequency of serious infections in patients receiving ofatumumab compared to placebo.

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