Rheumatoid Arthritis: Saag K

Kirwan J, Heiberg T, Hewlett S, Hughes R, Kvien T, Ahlmèn M, Boers M, Minnock P, Saag K, Shea B, Suarez Almazor M, Taal E. · University of Bristol Rheumatology Unit, Bristol Royal Infirmary, Bristol, UK. · J Rheumatol. · Pubmed #12672218 No free full text.

Abstract: The objective of the Patient Perspective Workshop at OMERACT 6 was to address the question of assessing the outcomes of intervention in rheumatoid arthritis (RA) from the perspective of those who experience the disease themselves. This was done by reviewing the current state of research in the area, identifying the requirements for the development of valid instruments, delineating a research agenda that can attain these requirements, and motivating participants to undertake the appropriate research. Through a series of meetings and discussion sessions a research agenda emerged that includes: exploring subjective experiences of RA identified by patients as important but not encompassed within the current "core set" of outcome measures (such as a sense of well being, fatigue, and disturbed sleep); clarifying terminology; and empowering patients to be more effective partners in outcomes research. These were supported by the OMERACT plenary session. Specific actions were required by both patient participants and organizers to ensure the nature of the conference, its focus and method of working were understood, and that the patient participants were sufficiently confident to make their contribution.

Furst DE, Saag K, Fleischmann MR, Sherrer Y, Block JA, Schnitzer T, Rutstein J, Baldassare A, Kaine J, Calabrese L, Dietz F, Sack M, Senter RG, Wiesenhutter C, Schiff M, Stein CM, Satoi Y, Matsumoto A, Caldwell J, Harris RE, Moreland LW, Hurd E, Yocum D, Stamler DA. · University of California at Los Angeles Medical School, CA 90024, USA. · Arthritis Rheum. · Pubmed #12209503 links to  free full text

Abstract: OBJECTIVE: To assess the efficacy, safety, and optimal dose of tacrolimus monotherapy in patients with rheumatoid arthritis (RA). METHODS: This phase II, randomized, double-blind, placebo-controlled monotherapy study was set in 12 community sites and 9 university-based sites. Two hundred sixty-eight patients with RA who were resistant to or intolerant of methotrexate (mean dose 15.2 mg/week) and had active disease for at least 6 months (mean tender joint count 28.2, mean erythrocyte sedimentation rate 46.5 mm/hour) were randomized to receive treatment after discontinuation of methotrexate. Those who received at least 1 dose of tacrolimus were analyzed; 141 completed the study. Stable dosages of nonsteroidal antiinflammatory drugs and low-dose prednisone were allowed during treatment. All patients were given 1, 3, or 5 mg of tacrolimus or placebo once daily for 24 weeks. The American College of Rheumatology definition of 20% improvement (ACR20) and the tender and swollen joint counts at the end of treatment were the primary outcomes. RESULTS: ACR20 response rates demonstrated a clear dose response. The ACR20 response was observed in 15.5% of patients receiving placebo (95% confidence interval [95% CI] 7.1-23.9%), 29% of the 1 mg tacrolimus group (95% CI 18.3-39.7%) (P < 0.058); 34.4% of the 3 mg group (95% CI 22.7-46.0%) (P < 0.013), and 50% of the 5 mg group (95% CI 37.8-62.3%) (P < or = 0.001). The tender joint count improved statistically significantly in all tacrolimus groups. The swollen joint count, physical function, and patient-assessed pain improved statistically significantly in the 3 mg and 5 mg groups. The incidence of creatinine elevation > or =40% above baseline levels increased in a dose-dependent manner. Dropout rates were high (41-59%) and were more common for inefficacy in the placebo patients (71.4%), whereas they were more common for toxicity in the high-dose tacrolimus groups (31-33%). Discontinuation for creatinine elevation occurred in the 3 mg (3.1%) and 5 mg (10.9%) tacrolimus groups. CONCLUSION: Tacrolimus improved disease activity in methotrexate-resistant or -intolerant patients with RA. A dose response was observed when efficacy and toxicity were assessed at different doses. The optimal dose of tacrolimus appears to be >1 mg but < or=3 mg daily.

Reid DM, Devogelaer JP, Saag K, Roux C, Lau CS, Reginster JY, Papanastasiou P, Ferreira A, Hartl F, Fashola T, Mesenbrink P, Sambrook PN, Anonymous00081. · University of Aberdeen, Aberdeen, UK. · Lancet. · Pubmed #19362675 No free full text.

Abstract: BACKGROUND: Persistent use of glucocorticoid drugs is associated with bone loss and increased fracture risk. Concurrent oral bisphosphonates increase bone mineral density and reduce frequency of vertebral fractures, but are associated with poor compliance and adherence. We aimed to assess whether one intravenous infusion of zoledronic acid was non-inferior to daily oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: This 1-year randomised, double-blind, double-dummy, non-inferiority study of 54 centres in 12 European countries, Australia, Hong Kong, Israel, and the USA, tested the effectiveness of 5 mg intravenous infusion of zoledronic acid versus 5 mg oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis. 833 patients were randomised 1:1 to receive zoledronic acid (n=416) or risedronate (n=417). Patients were stratified by sex, and allocated to prevention or treatment subgroups dependent on duration of glucocorticoid use immediately preceding the study. The treatment subgroup consisted of those treated for more than 3 months (272 patients on zoledronic acid and 273 on risedronate), and the prevention subgroup of those treated for less than 3 months (144 patients on each drug). 62 patients did not complete the study because of adverse events, withdrawal of consent, loss to follow-up, death, misrandomisation, or protocol deviation. The primary endpoint was percentage change from baseline in lumbar spine bone mineral density. Drug efficacy was assessed on a modified intention-to-treat basis and safety was assessed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00100620. FINDINGS: Zoledronic acid was non-inferior and superior to risedronate for increase of lumbar spine bone mineral density in both the treatment (least-squares mean 4.06% [SE 0.28] vs 2.71% [SE 0.28], mean difference 1.36% [95% CI 0.67-2.05], p=0.0001) and prevention (2.60% [0.45] vs 0.64% [0.46], 1.96% [1.04-2.88], p<0.0001) subgroups at 12 months. Adverse events were more frequent in patients given zoledronic acid than in those on risedronate, largely as a result of transient symptoms during the first 3 days after infusion. Serious adverse events were worsening rheumatoid arthritis for the treatment subgroup and pyrexia for the prevention subgroup. INTERPRETATION: A single 5 mg intravenous infusion of zoledronic acid is non-inferior, possibly more effective, and more acceptable to patients than is 5 mg of oral risedronate daily for prevention and treatment of bone loss that is associated with glucocorticoid use.

Mikuls T, Saag K, Criswell L, Merlino L, Cerhan JR. · Department of Medicine, University of Nebraska Medical Center and the Omaha VA Medical Center, Omaha, Nebraska 68198, USA. · J Rheumatol. · Pubmed #12734888 No free full text.

Abstract: OBJECTIVE: To examine the association of elderly onset rheumatoid arthritis (RA) with health related quality of life in a population based cohort of older women. METHODS: A nested case-control study of elderly onset RA within the Iowa Women's Health Study (IWHS), a prospective cohort established in 1986 of 41,000 women aged 55 to 69 years. A supplemental questionnaire was mailed to 122 RA cases and 1132 frequency matched controls from the cohort. We used unconditional logistic regression and linear regression to examine the association of elderly onset RA with self-reported measures of functional disability and quality of life. RESULTS: Elderly onset RA was associated with a 6-fold risk (OR 6.0, 95% CI 3.6-10.1) of significant functional disability (Health Assessment Questionnaire score (3) 1). Similarly, elderly onset RA was significantly associated with lower physical component scores of the Medical Outcome Study Short Form-12 (37.2 +/- 10.9 vs 43.6 +/- 11.6; p < 0.001). CONCLUSION: Among a community based cohort, elderly onset RA was strongly associated with functional disability and reduced quality of life. These associations were independent of other age associated factors including depression, recent fracture, and multiple comorbidities.

Kirwan JR, Minnock P, Adebajo A, Bresnihan B, Choy E, de Wit M, Hazes M, Richards P, Saag K, Suarez-Almazor M, Wells G, Hewlett S. · University of Bristol Academic Rheumatology Unit, and United Bristol Healthcare NHS Trust, Bristol, UK. · J Rheumatol. · Pubmed #17477482 No free full text.

Abstract: The Patient Perspective Workshop at OMERACT 8 considered evidence for the importance of fatigue to patients with rheumatoid arthritis (RA) and whether measurement of fatigue meets the requirements of the OMERACT filter. The workshop participants included 20 patients from 10 countries and 60 other OMERACT participants. Introductory papers and detailed notes for discussion group members set out the evidence from the literature and from recent analyses of clinical study data available to several participants. The workshop concluded that fatigue is a symptom that is important to patients, is commonly reported by patients, is often severe, can be measured by several current instruments that pass the OMERACT filter, is responsive to some interventions, and provides information additional to that commonly obtained from currently used outcomes. The final OMERACT plenary session endorsed by a very large majority (89%) the proposal that, in addition to the "core set" of outcome measures currently in widespread use, fatigue should be measured in future studies of RA whenever possible.