Clinical Newswire, December 15, 2009-Abatacept has a sustained efficacy and safety profile in patients with moderate to severe established rheumatoid arthritis (RA), but its effect in early RA when combined with the standard therapy methotrexate has not been explored. A study by R Westhovens, published in the December 2009 issue of the Annals of the Rheumatic Diseases, found that abatacept in combination with methotrexate had significantly higher clinical and radiographic efficacy compared with methotrexate alone in methotrexate-naive RA patients with poor prognosis.
Overall, 509 methotrexate-naive patients with RA for 2 or less years (mean disease duration of 6.5 months) participated in this randomized double blinded 2 year study. Patients had at least 12 tender and 10 swollen joints, C-reactive protein (CRP) of 0.45mg/dl or more, rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide type 2 (CCP2) seropositivity, and radiographic confirmation of bone erosion on the hands/wrists/feet. Patients were randomly assigned to receive abatacept (~10mg/kg) plus methotrexate (initially 7.5mg/week, increasing to 20mg/week from week 8, n=256) or placebo plus methotrexate (n=253) by intravenous infusion on days 1, 15 and 29 and monthly thereafter. Co-primary endpoints included remission at year 1, defined as a disease activity score in 28 joints (DAS28; CRP) of less than 2.6; and structural damage at year 1, assessed with Genant-modified Sharp scoring system total score (TS). Secondary endpoints included American College of Rheumatology (ACR)50 response, major clinical response (MCR), DAS28; CRP scores, Genant-modified Sharp erosion score (ES), and health assessment questionnaires that included the health assessment questionnaire disability index (HAQ-DI)20 and health-related quality of life (HRQoL) measured using the short form (SF)-36.
From day 57 until the end of the first year, a significantly higher number of patients in the combination abatacept/methotrexate group achieved DAS28 (CRP)-defined remission vs. the methotrexate group (41.4% vs. 23.3%, respectively; p<0.001). After 1 year, this group also had significantly reduced disease activity compared to patients treated with methotrexate alone; mean change from baseline in DAS28 (CRP) was -3.22 (+/- 0.09) and -2.49 (+/- 0.09) respectively (p<0.001).
Secondary endpoint measures after 1 year were also significantly improved in the abatacept/methotrexate group vs. patients given methotrexate alone, including ACR50 response (57.4% vs. 42.3%, respectively, p<0.001); ACR70 response (42.6 vs. 27.3, respectively, p<0.001); ACR90 response (16.4% vs. 6.7%, respectively, p=0.001); and major clinical response (MCR) (27.3% vs. 11.9%, respectively, p<0.001). Changes in TS and ES from baseline were lower at year 1 in the abatacept/methotrexate group vs. patients given methotrexate alone (p=0.040 and p=0.033, respectively). The proportion of patients exhibiting no radiologic progression was 62.2% (95% CI, 55.0-67.3) in the abatacept/methotrexate group and 52.9% (95% CI, 46.6-59.2) in the methotrexate group. Significant improvements in physical function and HRQoL after 1 year were also observed in the abatacept/methotrexate group vs. the methotrexate alone group (184 patients (71.9%) vs. 157 patients (62.1%), respectively, achieved a change from baseline of 0.3 units or more in HAQ-DI, p=0.024).
Both regimens had comparable safety profiles after 1 year, with 84.8% of patients displaying adverse events (3.1% leading to discontinuation) in the abatacept/methotrexate group compared with 83.4% (4.3% leading to discontinuation) in the methotrexate alone group. Infusional reactions occurred with more frequency in this group as well (6.3% vs. 2.0%), but were mild in severity. Rates of serious infections and autoimmune events were similar between groups and there were no cases of tuberculosis or opportunistic infections.
The authors concluded that abatacept plus methotrexate induced significantly higher DAS28(CRP)-defined remission and lower radiologic progression than methotrexatte alone, while maintaining similar safety profiles. The drug combination also was associated with significantly higher improvement in physical function and HRQoL. The authors commented that the positive results with abatacept plus methotrexate were particularly encouraging in light of the poor prognostic status of the patients, all of whom had erosions and were RF or anti-CCP2-seropositive at baseline. The authors cautioned that because study results were limited to 1 year, longer term structural changes or detection of infrequent safety-related events could not be adequately determined.
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