Rheumatoid Arthritis: Martin RW

Genovese MC, Bathon JM, Fleischmann RM, Moreland LW, Martin RW, Whitmore JB, Tsuji WH, Leff JA. · Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. · J Rheumatol. · Pubmed #15996057 No free full text.

Abstract: OBJECTIVE: To evaluate safety, efficacy, and radiographic progression in patients with early rheumatoid arthritis (RA) undergoing longterm treatment with etanercept. METHODS: Patients with early RA (disease duration of 3 years or less) who had completed a 2-year efficacy study comparing etanercept and methotrexate (MTX) were followed in an extension where they received 25 mg etanercept twice weekly. Safety was summarized descriptively and compared with data from the efficacy study. Efficacy and radiographic progression were assessed using American College of Rheumatology response criteria, disease activity scores, and Total Sharp Score (TSS). RESULTS: Rates of serious adverse events and serious infections did not increase with longterm exposure to etanercept, and were similar to rates reported for the blinded portion of the efficacy study. Efficacy was sustained in patients who completed 5 years of etanercept treatment at the time of this report (N = 201), even in those who decreased or discontinued use of MTX or corticosteroids. No radiographic progression (change in TSS < or = 0) was seen in 55% of patients with 5-year radiographs; negative change (TSS < 0) was seen in 11%. CONCLUSION: Etanercept treatment in patients with early RA was generally well tolerated for up to 5 years. The results indicate sustained efficacy and decreased rate of radiographic progression. The rate of radiographic progression was low compared with other studies, emphasizing the benefit gained in patients with early aggressive RA who undergo longterm treatment with etanercept.

Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Cannon GW, Spencer-Green G, Finck BK. · Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, 1000 Welch Road #203, Palo Alto, CA 94304, USA. · Arthritis Rheum. · Pubmed #12115173 links to  free full text

Abstract: OBJECTIVE: To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy. METHODS: In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner. Radiograph readers remained blinded to treatment group assignment and the chronologic order of images. RESULTS: At 24 months, more 25-mg etanercept patients than MTX patients met American College of Rheumatology 20% improvement criteria (72% and 59%, respectively; P = 0.005), and more had no increase in total score and erosion scores on the Sharp scale (P = 0.017 and P = 0.012, respectively). The mean changes in total Sharp score and erosion score in the 25-mg etanercept group (1.3 and 0.66 units, respectively) were significantly lower than those in the MTX group (3.2 and 1.86 units, respectively; P = 0.001). Significantly more patients in the 25-mg etanercept group (55%) than in the MTX group (37%) had at least 0.5 units of improvement in the Health Assessment Questionnaire disability index (P < 0.001). Fewer patients in the etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events. CONCLUSION: Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.

Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Genovese MC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Finck BK. · Johns Hopkins Asthma and Allegy Center, Johns Hopkins University, Baltimore, MD 21224, USA. · N Engl J Med. · Pubmed #11096165 links to  free full text

Abstract: BACKGROUND: Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown. METHODS: We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months. Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale. On this scale, an increase of 1 point represents one new erosion or minimal narrowing. RESULTS: As compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, 50 percent, and 70 percent improvement in disease activity during the first six months (P<0.05). The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group (P= 0.001), and the respective increases during the first 12 months were 0.47 and 1.03 (P=0.002). Among patients who received the 25-mg dose of etanercept, 72 percent had no increase in the erosion score, as compared with 60 percent of patients in the methotrexate group (P=0.007). This group of patients also had fewer adverse events (P=0.02) and fewer infections (P= 0.006) than the group that was treated with methotrexate. CONCLUSIONS: As compared with oral methotrexate, subcutaneous [corrected] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis.

Martin RW, Head AJ, René J, Swartz TJ, Fiechtner JJ, McIntosh BA, Holmes-Rovner M. · Departments of Medicine and Rheumatology, College of Human Medicine, Michigan State University, Grand Rapids, Michgan 49546, USA. · J Rheumatol. · Pubmed #18278840 No free full text.

Abstract: OBJECTIVE: To explore how rheumatoid arthritis (RA) antirheumatic drug-specific knowledge and numeric literacy, patient trust in physician, and demographic and disease-related factors relate to the confidence of patient decision-making related to disease modifying antirheumatic drugs (DMARD). METHODS: Data were analyzed from 628 randomly selected patients with RA receiving care in community rheumatology practices, who responded to a multicenter, cross-sectional mail survey. We used multiple regression models to predict patient confidence in DMARD decision-making related to their most recently initiated DMARD. RESULTS: Significant positive correlation was found between confidence in DMARD decision and trust in physician, DMARD-specific knowledge, and disease duration, but not risk-related numeric literacy, sex, or education. Negative correlations were found with disease severity and current bother with DMARD side effects. A multiple linear regression model of confidence in DMARD decision had an overall R = 0.788, R2 = 0.620 (p < 0.001). The 4 dependent variables contributing significantly to the model were female sex, Medicaid insurance status, satisfaction with RA disease control, and trust in physician, with standardized beta = 0.077, -0.089, 0.147, and 0.687, respectively. CONCLUSION: In this sample of community patients with RA, the patient trust in physician had substantially greater effect on confidence in DMARD decision than DMARD-specific knowledge, disease-related factors, or demographic characteristics.

Gazi H, Pope JE, Clements P, Medsger TA, Martin RW, Merkel PA, Kahaleh B, Wollheim FA, Baron M, Csuka ME, Emery P, Belch JF, Hayat S, Lally EV, Korn JH, Czirjak L, Herrick A, Voskuyl AE, Bruehlmann P, Inanc M, Furst DE, Black C, Ellman MH, Moreland LW, Rothfield NF, Hsu V, Mayes M, McKown KM, Krieg T, Siebold JR. · Division of Rheumatology, Department of Medicine, The University of Western Ontario, London, Ontario, Canada. · J Rheumatol. · Pubmed #17299843 No free full text.

Abstract: OBJECTIVE: To obtain a consensus on the minimal clinically relevant treatment effect in various scleroderma disease outcome measures to be used in future clinical trials. METHODS: A Delphi consensus building exercise using a survey was sent out to members of the Scleroderma Clinical Trials Consortium (SCTC). The 65 SCTC members were divided into 2 groups. Group 1 was informed, in a cover letter, of the usual American College of Rheumatology 20% response results in randomized trials using effective biologic treatments for rheumatoid arthritis, while Group 2 was not. The first round of the exercise presented the scleroderma experts with a survey composed of 95 questions/clinical scenarios divided into 8 categories. These included situations where the treatment group improved, or worsened, or where some outcome measures improved, while others worsened. From the responses of this first round, a mean, mode, median, and range of responses for each of the 95 questions was obtained. This information was sent out, in the second round of the Delphi exercise, only to those respondents who answered the first round. The respondent's previous answer and the mean and range from the first round were provided for each question. It gave respondents the option to change any of their initial responses. The median of their responses in the second round was used to calculate the values for the minimal clinically relevant treatment effect. RESULTS: Thirty-two of the 65 SCTC members returned the first round of the Delphi exercise. Twenty-eight members returned the second round. Intraclass correlation coefficients between responses to round 1 and 2 were calculated for the questions. These varied from 0.99 (excellent agreement) to 0.02 (poor agreement). The p value was under 0.09 for 9 questions and under 0.19 for 20 questions. Standard deviations (SD) were calculated and were found to be lesser for each of the questions in round 2 when compared to the SD in responses from round 1, thus indicating a movement towards a consensus by the second round. An average of 33% of the responses were changed by the respondents in the second round of the Delphi exercise to a value closer to the median/average of the first round's responses. A range in required values for the minimal clinically relevant treatment effect for Modified Rodnan skin score is 3 to 7.5 units, Health Assessment Questionnaire Disability Index (HAQ-DI) 0.2 to 0.25 units, HAQ pain 0.2 to 0.3 units, MD global (100 mm visual analog scale) 8 to 13, patient global assessment 10 to 12, and diffusing capacity (percentage predicted) 9 to 10. The scenarios were especially weighted towards overall disease modification, thus organ-specific measures, such as 6 minute walk time (which has been used in many pulmonary artery hypertension trials), forced vital capacity, and a dyspnea rating (which may be important in scleroderma lung trials), were not included in the survey. CONCLUSION: Our study begins to address the current deficiency in our knowledge of appropriate values for the minimal clinically relevant treatment effect in various scleroderma disease outcome measures. A consensus could be achieved, or at least a range of minimal clinically relevant treatment effect values could be found for several outcome measurements. Of course, this consensus statement will be modified by evidence as it accrues in each consensus area.

Moreland LW, Weinblatt ME, Keystone EC, Kremer JM, Martin RW, Schiff MH, Whitmore JB, White BW. · Clinical Immunology and Rheumatology,University of Alabama at Birmingham, Birmingham, AL 35294-7201, USA. · J Rheumatol. · Pubmed #16541481 No free full text.

Abstract: OBJECTIVE: To evaluate safety and efficacy of longterm etanercept treatment in patients with disease modifying antirheumatic drug (DMARD) refractory rheumatoid arthritis (RA). METHODS: Safety results are reported for 714 patients who received etanercept in one of 7 initial trials or a longterm extension. Efficacy results are reported for 581 patients who enrolled in the extension. RESULTS: Of the 714 patients enrolled in the initial trials, 581 (81%) enrolled in the extension, and 388 (54%) patients are continuing to receive etanercept therapy. The longest individual treatment was 8.2 years, with 3139 total patient-years of etanercept exposure. Rates of serious adverse events (overall rate=14.8 events/100 patient-yrs), serious infections (overall rate=4.2 events/100 patient-yrs), cancer (overall rate=1.0 events/100 patient-yrs), and deaths (overall rate=0.7 events/100 patient-yrs) were stable each year, through 8 years of etanercept exposure. For 356 patients who completed 6 years of etanercept treatment, response rates were ACR20=73%, ACR50=52%, ACR70=27%, DAS28 CRP good response=52%, and DAS28 CRP remission=37% of patients. Similar responses occurred in 167 patients who completed Year 7. Doses of concomitant methotrexate or corticosteroids were reduced in many patients who maintained clinical responses. CONCLUSION: The safety profile of etanercept was consistent over time, with rates of adverse events similar to those reported for patients with RA in general. Durable clinical responses were observed in some patients for 7 years or more. The benefit-to-risk ratio for longterm etanercept treatment remains highly favorable.

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.