Rheumatoid Arthritis: Tannenbaum H

Tannenbaum H, Peloso PM, Russell AS, Marlow B. · Rheumatic Disease Centre of Montreal, Montreal General Hospital; McGill University, Montreal, Canada. · Can J Clin Pharmacol. · Pubmed #11011110 No free full text.

Abstract: The Second Canadian Consensus Conference was convened to discuss the latest developments in the management of osteoarthritis (OA) and rheumatoid arthritis (RA), and to make evidence-based recommendations, specifically regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for these indications in primary care practice. The recent availability of cyclo-oxygenase-2-specific inhibitors has raised questions as to their role in the pharmacological management of OA and RA, particularly in relation to conventional treatments such as acetaminophen and nonspecific NSAIDs (with or without misoprostol or proton pump inhibitors). The recommendations in this document, which were arrived at through critical review of data from published randomized, clinical trials, deal with treatments of choice, information to discuss with patients, use of NSAIDs in patients at risk for serious upper gastrointestinal complications, renal or hepatic impairment or congestive heart failure, appropriate follow-up, and the use of NSAIDs with anti- hypertensives, warfarin, low dose acetylsalicylic acid and other medications. The goal of these recommendations is to improve patient outcomes in the primary care setting by maximizing treatment efficacy and minimizing rates of adverse events.

Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, Fischkoff SA, Chartash EK. · University of Toronto, Toronto, Ontario M5G 1X5, Canada. · Arthritis Rheum. · Pubmed #15146409 links to  free full text

Abstract: OBJECTIVE: Tumor necrosis factor (TNF) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human anti-TNF monoclonal antibody, to inhibit the progression of structural joint damage, reduce the signs and symptoms, and improve physical function in patients with active RA receiving concomitant treatment with methotrexate (MTX). METHODS: In this multicenter, 52-week, double-blind, placebo-controlled study, 619 patients with active RA who had an inadequate response to MTX were randomized to receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant MTX. The primary efficacy end points were radiographic progression at week 52 (total Sharp score by a modified method [TSS]), clinical response at week 24 (improvements of at least 20% in the American College of Rheumatology core criteria [ACR20]), and physical function at week 52 (disability index of the Health Assessment Questionnaire [HAQ]). RESULTS: At week 52, there was statistically significantly less radiographic progression, as measured by the change in TSS, in the patients receiving adalimumab either 40 mg every other week (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8 +/- 4.9) as compared with that in the placebo group (2.7 +/- 6.8) (P < or = 0.001 for each comparison). In addition, there were statistically significant changes in the components of the TSS. At week 24, ACR20 responses were achieved by 63% and 61% of patients in the adalimumab 40 mg every other week and 20 mg weekly groups, respectively, versus 30% of patients in the placebo group (P < or = 0.001 for each comparison). At week 52, ACR20 responses were achieved by 59% and 55% of patients taking adalimumab 40 mg every other week and 20 mg weekly, respectively, versus 24% of patients taking placebo (P < or = 0.001 for each comparison). At week 52, physical function as measured by the HAQ demonstrated statistically significant improvement with adalimumab 40 mg every other week and 20 mg weekly compared with placebo (mean change in HAQ score -0.59 and -0.61, respectively, versus -0.25; P < or = 0.001 for each comparison). A total of 467 patients (75.4%) completed 52 weeks of treatment. Adalimumab was generally well tolerated. Discontinuations occurred in 22.0% of adalimumab-treated patients and in 30.0% of placebo-treated patients. The rate of adverse events (both serious and nonserious) was comparable in the adalimumab and placebo groups, although the proportion of patients reporting serious infections was higher in patients receiving adalimumab (3.8%) than in those receiving placebo (0.5%) (P < or = 0.02), and was highest in the patients receiving 40 mg every other week. CONCLUSION: In this 52-week trial, adalimumab was more effective than placebo at inhibiting the progression of structural joint damage, reducing the signs and symptoms, and improving physical function in patients with active RA who had demonstrated an incomplete response to MTX.

Bruyn GA, Tate G, Caeiro F, Maldonado-Cocco J, Westhovens R, Tannenbaum H, Bell M, Forre O, Bjorneboe O, Tak PP, Abeywickrama KH, Bernhardt P, van Riel PL, Anonymous00077. · Medisch Centrum Leeuwarden (Zuid), Afd. Reumatologie, Leeuwarden, 8934 AD, The Netherlands. · Ann Rheum Dis. · Pubmed #18037627 No free full text.

Abstract: OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.

Tannenbaum H, Bombardier C, Davis P, Russell AS, Anonymous00204. · Rheumatic Disease Centre of Montreal, Montreal General Hospital, McGill University, Montreal, Quebec, Canada. · J Rheumatol. · Pubmed #16331802 No free full text.

Abstract: OBJECTIVE: To revisit our previous evidence-based recommendations on the appropriate prescription of nonsteroidal antiinflammatory drugs (NSAID) with particular emphasis on cyclooxygenase-2 selective inhibitors (coxibs). METHODS: Needs assessments were conducted among Canadian physicians to determine their educational needs surrounding NSAID/coxibs. A survey of patients with arthritis was also conducted. Consensus participants reviewed articles relating to NSAID/coxibs in peer-reviewed journals between January 2000 and December 2004. At the consensus meeting, held January 21-23, 2005, participants discussed selected topics, after which recommendations were formulated and debated. Results. At the time of the meeting, it was agreed that emerging cardiovascular data were not clear enough to decide whether unanticipated cardiovascular events associated with coxibs represent a class effect or an effect of an individual drug. However, publications that appeared shortly after the meeting, as well as data presented at both the Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the US Food and Drug Administration, February 16-18, 2005, and Health Canada's Expert Advisory Panel on the Safety of Cox-2 Selective NSAID, June 9-10, 2005, clarified that all available coxibs do carry some degree of cardiovascular risk, denoting a class effect. Our consensus group made the following specific recommendations: (1) Patients should be fully informed about treatment options, including the need to balance between cardiovascular risks and gastrointestinal (GI) benefits of NSAID/coxibs. (2) Coxibs are as effective as nonselective NSAID and superior to acetaminophen for the symptoms of arthritis. Topical NSAID may also be beneficial. (3) Coxibs are associated with fewer severe GI complications than nonselective NSAID. A proton pump inhibitor (PPI) should be prescribed if an NSAID must be used in a patient at increased GI risk. (4) The renal/blood pressure (BP) impact of coxibs is similar to that of NSAID. (5) In individuals at risk, creatinine clearance and BP should be determined at baseline and shortly after treatment begins. (6) In the geriatric population, use of nonpharmacological therapies should be maximized, and special caution is required before prescribing oral NSAID/coxibs. (7) Patients taking rofecoxib have been shown to have an increased risk of cardiovascular events. Current data suggest that this increased cardiovascular risk may be an effect of the NSAID/coxib class. (8) Although the data are limited, coxibs may be more cost-effective for patients at high GI risk than nonselective NSAID plus proprietary PPI. CONCLUSION: Coxibs continue to be an option in the treatment armamentarium. Given the evolving cardiovascular information, physicians and patients should weigh the benefits and risks of NSAID/coxib treatment. This concern emphasizes the need to routinely reassess patients' risks. These recommendations, which were formulated according to the Appraisal of Guidelines for Research and Evaluation, are intended to be used as guidelines to supplement, but not replace, the physician's judgment in clinical decision-making.