Rheumatoid Arthritis: Schiff MH

Gibofsky A, Palmer WR, Goldman JA, Lautzenheiser RL, Markenson JA, Weaver A, Schiff MH, Keystone EC, Paulus HE, Harrison MJ, Whitmore JB, Leff JA. · Department of Rheumatology, Hospital for Special Surgery, New York, NY, USA. · Curr Med Res Opin. · Pubmed #16393443 No free full text.

Abstract: OBJECTIVE: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice. RESEARCH DESIGN AND METHODS: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5-year study. RESULTS: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy. CONCLUSIONS: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001-2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.

Hansen KE, Hildebrand JP, Genovese MC, Cush JJ, Patel S, Cooley DA, Cohen SB, Gangnon RE, Schiff MH. · Division of Rheumatology, University of Wisconsin, Madison, Wisconsin, USA. · J Rheumatol. · Pubmed #15170921 No free full text.

Abstract: OBJECTIVE: To describe the degree of clinical benefit in patients with rheumatoid arthritis (RA) who receive infliximab therapy after lack of efficacy with etanercept. METHODS: In a retrospective study among 6 centers primarily designed to assess the safety of infliximab in combination with leflunomide, a standardized chart review form was used to collect data on 93 patients with RA. During that study, it was noted that some of these patients had switched from etanercept to infliximab. In this study, we compared the response of subjects switching from etanercept to infliximab (n = 20) to that of subjects receiving infliximab with no prior tumor necrosis factor (TNF) therapy (n = 73). RESULTS: The swollen and tender joint count, patient and physician global assessments, morning stiffness, and C-reactive protein all improved substantially in both groups, with no statistical difference in the degree of benefit between the groups. At the time of chart review, switchers had received a statistically higher dose of infliximab than controls (4.4 vs 3.19 mg/kg; p = 0.006) with a total of 5.7 and 5 infusions, respectively. CONCLUSION: In this retrospective study, previous lack of efficacy with etanercept did not predict lack of efficacy with infliximab. Indeed, the degree of clinical improvement was similar in both groups, although switchers were receiving a higher dose of infliximab at the time of chart review. Our findings suggest that clinical response may differ between anti-TNF agents, and lack of response to one agent may not predict a lack of response to another.

Schiff MH, Strand V, Oed C, Loew-Friedrich I. · Department of Clinical Medicine, University of Colorado School of Medicine and Denver Arthritis Clinic, Denver, Colorado 80220, USA. · Drugs Today (Barc). · Pubmed #12861359 No free full text.

Abstract: Leflunomide is a new disease modifying antirheumatic drug (DMARD) that inhibits lymphocyte proliferation by blocking dihydroorotate dehydrogenase (DHODH), the enzyme critical for the production of pyrimidine necessary for DNA synthesis. Through this mode of action, leflunomide inhibits the lymphocyte proliferation associated with the clonal expansion of T cells in rheumatoid arthritis (RA). In clinical trials, leflunomide was superior to placebo and comparable to sulfasalazine and methotrexate for improving both the signs and symptoms of RA. Leflunomide was also superior to placebo and sulfasalazine and comparable to methotrexate in overall improvement of physical function. Leflunomide was equivalent to methotrexate and sulfasalazine in retarding disease progression measured radiographically. Due to its unique mode of action in the treatment of RA, leflunomide shows value in combination therapy with methotrexate for patients refractory to methotrexate alone. The most common adverse reactions associated with leflunomide therapy include gastrointestinal symptoms, allergic reactions, reversible alopecia and elevated liver enzymes. Adverse events were generally mild to moderate, and resolved without complication. The results of phase II and phase III clinical trials indicate that leflunomide is a safe and efficacious drug for the treatment of RA.

Fleischmann RM, Baumgartner SW, Tindall EA, Weaver AL, Moreland LW, Schiff MH, Martin RW, Spencer-Green GT. · University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. · J Rheumatol. · Pubmed #12672185 No free full text.

Abstract: OBJECTIVE: Approximately 3% of the US population over the age of 65 years has rheumatoid arthritis (RA). We compared the safety and efficacy of etanercept (Enbrel) in patients with RA who were > or = 65 years to those < 65 years in open-label and double-blind, randomized clinical trials. METHODS: Patients from 4 double-blind, randomized controlled trials and 5 open-label trials were included in this retrospective analysis. Patients were grouped by age (< 65 or > or = 65 yrs) at time of study entry. All patients received etanercept subcutaneously twice weekly. Improvement in signs and symptoms was assessed by the proportion of patients who achieved the American College of Rheumatology definition of improvement (ACR 20). The ACR 50 and ACR 70 responses were calculated in an analogous fashion. Safety was assessed at regularly scheduled visits. RESULTS: Of 1128 patients enrolled in etanercept trials, 197 (17%) were > or = 65 years of age. Clinical response was rapid and sustained and did not differ between age groups. At one year, 69% of patients < 65 years and 66% of patients > or = 65 years met the ACR 20. Forty percent of the patients > or = 65 years met the ACR 50 and 17% met the ACR 70. Etanercept was well tolerated. Although injection site reactions, headache, and rhinitis occurred somewhat more frequently in younger patients, the overall rates and types of other adverse events were comparable in both groups. CONCLUSION: Etanercept is a new treatment option for older patients with RA and has substantial benefit and comparable safety regardless of patient age.

Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G, van Riel PL, Tugwell P. · University of Vienna and Lainz Hospital, Austria. · Rheumatology (Oxford). · Pubmed #12595618 links to  free full text

Abstract: OBJECTIVE: The objective of this study was to verify the usefulness of a simple disease activity index (SDAI) for rheumatoid arthritis (RA). METHODS: The SDAI is the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity [visual analogue scale (VAS) 0-10 cm] and level of C-reactive protein (mg/dl, normal <1 mg/dl). Analysis initially focused on MN301, one of the three phase III clinical trials of leflunomide, in order to assess possible correlations between the SDAI and the Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 (DAS 28). Results were then compared with the other two trials, MN302 and US301. A total of 1839 patients were evaluated. At baseline, 6 and 12 months, the SDAI, DAS 28, American College of Rheumatology (ACR) response criteria and mean HAQ scores were determined for each patient and compared by linear regression for significant correlation. The SDAI was compared qualitatively to the ACR 20% at 3, 6 and 12 months. The index was further validated by comparing the SDAI with survey results obtained from rheumatologists' evaluations of disease activity in test cases. The survey results included defining categorical changes in the SDAI indicating major, minor or no improvement in disease activity in response to treatment. Changes in total Sharp score at 6 and 12 months of treatment were determined for each of these categories of the SDAI and for comparable categories of the DAS 28. RESULTS: The mean SDAI calculated for patients at baseline in study MN301 was 50.06 (range 25.10-96.10) and was, respectively, 50.55 (range 22.10-98.10) and 43.20 (range 12.90-78.20) in studies MN302 and US301. In all three trials, the SDAI was correlated with a high level of statistical significance to the DAS 28 and HAQ scores at baseline, endpoint and change at endpoint. Patients achieving the ACR 20, 50, 70 or 90% response showed proportionate changes in the SDAI. Analysis of surveyed physician responses showed a significant association between the perception of disease activity and the SDAI, as well as changes in the SDAI. Qualitative analysis of radiographic progression at 6 and 12 months for patients showing either major, minor or no improvement of the SDAI showed correspondingly larger increases of the total Sharp score at 12 months. CONCLUSION: The SDAI is a valid and sensitive assessment of disease activity and treatment response that is comparable with the DAS 28 and ACR response criteria; it is easy to calculate and therefore a viable tool for day-to-day clinical assessment of RA treatment. Overall results indicate that the SDAI has content, criterion and construct validity.

Schiff MH. · No affiliation provided · Arthritis Rheum. · Pubmed #15641081 links to  free full text

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