ADALIMUMAB INHIBITS THE PROGRESSION OF STRUCTURAL JOINT DAMAGE IN PATIENTS WITH ACTIVE RA

E. Keystone , A.F. Kavanaugh , J. Sharp , H. Tannenbaum , L. Teoh , S. Fischkoff , E. Chartash Centre for Advanced Therapeutics, Mount Sinai Hospital, Toronto, Canada, Rheumatology Div., UCSD, La Jolla, Bainbridge Island, United States, , Rheumatic Disease Centre of Montreal, Montreal, Canada, ImmunoScience Development Center, Abbott Laboratories, Parsippany, United StatesObjectives: This study evaluated the ability of adalimumab (HUMIRA, Abbott) treatment to inhibit the radiographic progression, and to improve quality of life outcomes and the signs and symptoms of rheumatoid arthritis (RA) in patients with active RA who were partial responders to methotrexate (MTX) therapy.Methods: In this 52-week, double-blind, randomized, placebo-controlled trial, patients with active RA who had partial efficacy with MTX on stable doses of MTX were randomly assigned to receive subcutaneous (sc) adalimumab 20 mg weekly, 40 mg every other week (eow) with placebo on alternate weeks, or placebo weekly. Patients remained on a stable dose of MTX. X-ray films, which were taken at baseline, and at 24 and 52 weeks were digitized and scored by two readers who were blinded to study treatment and the chronological order of the images.Results: A total of 619 patients were randomized. Mean baseline characteristics included: age 57 years, 75% female, disease duration 11 years, modified total Sharp x-ray score 69.2, tender joint count (TJC) 28, swollen joint count (SJC) 19, C-reactive protein (CRP) 1.7 mg/dL, health assessment questionnaire (HAQ) 1.5, and MTX dose 16.6 mg/week.At week 52, in addition to significant improvement in clinical measures of disease activity, there were significant differences between adalimumab and placebo in radiographic end points (table), indicating inhibition of the progression of structural joint damage with adalimumab treatment. Similar findings were observed for radiographic endpoints in patients treated with adalimumab 40 mg eow or 20 mg weekly. Patients treated with adalimumab 40 mg eow or 20 mg weekly had significantly smaller changes in their modified total Sharp x-ray scores (0.1 and 0.8, respectively) than patients who received placebo (2.7) (p≤0.001). Significantly smaller changes in erosion scores were also reported in patients treated with 40 mg eow or 20 weekly adalimumab at week 52, as compared to placebo (p≤0.001). Joint space narrowing scores were significantly smaller in patients treated with 40 mg eow adalimumab at week 52, as compared to placebo (p≤0.001).Additionally at this same time point (week 52), no new erosions were observed in significantly more patients taking adalimumab 40 mg eow (61.8%) or 20 mg weekly (57.9%) than placebo (46.0%) (p≤0.05 and p≤0.001, respectively). Both adalimumab dose groups were associated with statistically significant (p≤0.001) improvements in observed disability index of the HAQ (-0.64 and -0.69, respectively) compared to placebo (-0.34) after 52 weeks of treatment. ACR20, ACR50, and ACR70 response rates at week 24 were significantly greater with adalimumab 40 mg eow (63%, 39%, and 21%) and adalimumab 20 mg weekly (61%, 41%, and 18%) than with placebo (30%, 10%, and 3%) (p≤0.001). Withdrawals due to AEs occurred in 10.0% of adalimumab patients and 6.5% of placebo patients. Endpoint Adalimumab Placebo 40 mg eow 20 mg weekly (n=207) (n=212) (N=200) Modified Sharp X-ray score Mean baseline score 72.1 66.4 66.4 Mean (median) change at week 52 0.1* (0.0) 0.8* (0.0) 2.7 (1.0) Erosion score Mean (median) change at week 52 0.0* (0.0) 0.4* (0.0) 1.7 (0.5) Joint space narrowing score Mean (median) change at week 52 0.1* (0.0) 0.5 (0.0) 1.1 (0.0) *Statistically significantly different from placebo (p≤0.001) based on median values. atistically significantly different from placebo (p≤0.001) based on median values.Conclusion: Adalimumab given sc every other week (40 mg) or weekly (20 mg) with concomitant MTX significantly inhibited the progression of structural joint damage, reduced the disability and improved the signs and symptoms of RA in patients who were partial responders to MTX.Citation: , volume , supplement , year 2003, page Session: Rheumatoid arthritis – Treatment