Rheumatoid Arthritis: Blumenauer B

Blumenauer B, Judd M, Cranney A, Burls A, Coyle D, Hochberg M, Tugwell P, Wells G. · No affiliation provided · Cochrane Database Syst Rev. · Pubmed #14584021 No free full text.

Abstract: BACKGROUND: Etanercept is a soluble tumour necrosis factor alpha-receptor DMARD for the treatment of rheumatoid arthritis (RA). OBJECTIVES: To assess the efficacy and safety of etanercept for the treatment of RA. SEARCH STRATEGY: Five electronic databases were searched from 1966 to February 2003 with no language restriction. SELECTION CRITERIA: All randomized controlled trials (minimum 6 month duration) comparing three possible combinations 1) etanercept (10 mg or 25 mg twice weekly) with methotrexate (MTX) to MTX alone 2) etanercept to MTX, or 3) etanercept to placebo were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed the methodological quality of the trails. The American College of Rheumatology (ACR) core set of disease activity measures for RA clinical trials, radiographic, withdrawals and toxicity outcomes were analyzed. MAIN RESULTS: Three trials were included in this review. Two trials compared an experimental group who were started on etanercept compared to a control group; both groups had the same ongoing background therapy of nonsteroidals in both trials plus in one trial one group was on stable methotrexate.In these two trials the ACR 20, ACR 50 and ACR 70 response rates at 6 months were statistically significantly and clinically important with etanercept 25 mg subcutaneous injections (SC) twice weekly. Sixty-four percent of people receiving etanercept ache vied an ACR 20 response compared to 15% of controls and the number needed to treat (NNT) with etanercept is 2 people. Thirty-nine percent of those receiving etanercept achieved an ACR 50 response compared to 4% of taking control treatment and the NNT is three.Fifteen percent of people taking etanercept achieved an ACR 70 compared to 1% of controls with a NNT of 7 people.In the third trial of starting etanercept compared to starting methotrexate the number of participants who achieved an ACR 20, 50 or response at 6 and 12 months were not statistically significant for either etanercept dose.Etanercept treatment showed a statistically significantly and clinically important affect on joint damage as measured by the Sharp erosion score. Among participants who received etanercept 72% had no increase in their erosion score compared to 60% of participants in the methotrexate group. Withdrawal and toxicity results were acceptable. REVIEWER'S CONCLUSIONS: Etanercept 25 mg SC twice weekly was more efficacious than control treatment for ACR 20, 50 and 70 at 6 months, and over 12 months it slowed joint damage.

Blumenauer B, Cranney A, Clinch J, Tugwell P. · Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada. · Pharmacoeconomics. · Pubmed #12959625 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic, disabling, inflammatory polyarthritis that affects patient well-being and QOL. Many disease-modifying antirheumatic drugs (DMARDs) are available for treating RA but patients are often refractory to treatment. The goal of treatment is to improve both general health and health-related QOL. Generic and disease-specific instruments exist to measure QOL. Using these instruments, one can determine if QOL improves with treatment. If the minimal clinically important difference (MCID) for the instrument is known, one can determine if the change is clinically significant. The literature was reviewed in a systematic manner to determine which drugs could affect QOL in patients with refractory RA. Refractory RA is poorly defined but we used the definition of failing at least two DMARDs. Methotrexate, leflunomide, cyclosporin, glucocorticoids, etanercept and infliximab clinically and statistically significantly improved QOL in patients with RA. Gold and epoetin-alpha (erythropoietin) statistically improved QOL in patients with RA but the clinical significance of the improvements could not be determined. These studies were either in non-refractory populations or the refractoriness could not be determined. Further study is required to determine the response of QOL to treatment in patients with refractory RA and instruments with known MCIDs should be used so that the clinical significance of the improvement can be determined.

Blumenauer B, Judd M, Wells G, Burls A, Cranney A, Hochberg M, Tugwell P. · Department of Rheumatology, Ottawa Hospital, University of Ottawa. · Cochrane Database Syst Rev. · Pubmed #12137712 No free full text.

Abstract: BACKGROUND: Infliximab is a human murine chimeric anti-tumour necrosis factor alpha monoclonal antibody recently approved for the treatment of refractory RA. OBJECTIVES: To assess the efficacy and safety of infliximab for the treatment of rheumatoid arthritis. SEARCH STRATEGY: Electronic databases including Biological Abstracts, CINAHL, Current Contents, Dissertation Abstracts, EBM Reviews, HealthSTAR and MEDLINE were searched from 1966 to March 2002. Rheumatoid arthritis was searched as an exploded MESH heading. Infliximab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. The specific search strategy is shown below. SELECTION CRITERIA: All randomized controlled trials comparing infliximab 1, 3, 5 or 10 mg/kg with methotrexate(MTX) to MTX alone, or without MTX to placebo, with a minimum duration of 6 months and at least 2 infusions were eligible. DATA COLLECTION AND ANALYSIS: Data was extracted by 2 independent reviewers and the methodological quality of the trials was assessed using a validated assessment tool scale. Outcome variables included the ACR core set of disease activity measures for RA clinical trials and radiographic outcome data. Withdrawals and toxicity were also included. End of trial results were pooled. Continuous data were pooled using weighted mean differences and dichotomous data using relative risks. MAIN RESULTS: Two trials with a total of 529 patients met the inclusion criteria. Patients fulfilling the American Rheumatism Association 1987 RA diagnostic criteria were randomized to receive either infliximab 1mg/kg (with and without MTX), 3mg/kg(with and without MTX), 10mg/kg of infliximab (with and without MTX) or placebo infusion plus MTX. Infusions were given every 4 or 8 weeks. After 6 months ACR 20, ACR 50 and ACR 70 response rates were significantly improved in all infliximab doses compared to control. The number needed to treat with infliximab to achieve an ACR 20, 50 or 70 response in patients with refractory RA under specialist care ranged from 2.9 to 3.3 for ACR 20, 3.6 to 4.8 for ACR 50 and 5.9 to 12.5 for ACR 70 depending on the dose (3mg/kg or 10mg/kg given either every 4 or 8 weeks). Total withdrawals and withdrawals due to lack of efficacy were lower for all doses of infliximab versus controls. Withdrawals for adverse events and withdrawals for other reasons were not statistically significantly different for those receiving infliximab from control. REVIEWER'S CONCLUSIONS: Treatment with infliximab for 6 and 12 months significantly reduces RA disease activity and appeared to have an acceptable safety profile in these trials. Total radiographic scores improved, fewer patients showed radiographic progression, and more patients showed radiographic improvement with infliximab treatment at 12 months compared to controls. However, only 2 trials met the inclusion criteria, and these results are largely driven by the largest trial. The available efficacy and toxicity data is relatively short-term (6-12 months). In order to detect rare events that may be associated with infliximab, larger and longer term studies are required.

Blumenauer B, Coyle D, Tugwell P. · Faculty of Medicine, University of Ottawa, Ottawa, Canada. · Expert Opin Pharmacother. · Pubmed #11934345 No free full text.

Abstract: Rheumatoid arthritis affects ~ 1% of the population. It is associated with pain, deformity, decreased quality of life and disability that in turn affects patients' ability to work. A variety of disease-modifying antirheumatic drugs are available to control the disease activity of rheumatoid arthritis. The goal of treatment is to improve patients' quality of life and prevent joint destruction. This paper reviews both the clinical aspects of frequently prescribed disease-modifying antirheumatic drugs and the available cost-effectiveness information. Clinical evidence supports the effectiveness of methotrexate, etanercept, infliximab, gold, hydroxychloroquine, leflunomide, sulfasalazine, penicillamine, cyclosporin, azathioprine and corticosteroids. The last four of these are associated with greater toxicity and are only used if less toxic drugs are ineffective. The lack of published economic evaluations of disease-modifying antirheumatic drugs highlights the need for such studies to allow efficacious and cost-effective drugs to be used to prevent the long-term complications of uncontrolled rheumatoid arthritis.