Rheumatoid Arthritis: Fitzcharles MA

Tsakonas E, Fitzgerald AA, Fitzcharles MA, Cividino A, Thorne JC, M'Seffar A, Joseph L, Bombardier C, Esdaile JM. · Department of Medicine, McGill University, Montreal, Quebec, Canada. · J Rheumatol. · Pubmed #10743799 No free full text.

Abstract: OBJECTIVE: To assess the longterm effect of delaying therapy with second-line agents in patients with early rheumatoid arthritis (RA). METHODS: One hundred nineteen patients who participated in a 9 month placebo controlled randomized trial of hydroxychloroquine sulfate (HCQ) were followed prospectively for an additional 3 years. Those randomized to HCQ are referred to as the early treatment group and those randomized to placebo as the delayed treatment group. Participants were assessed annually for pain [Arthritis Impact Measurement Scales (AIMS) and Stanford Health Assessment Questionnaire (HAQ)], physical disability (AIMS and HAQ), and the RA global well being scale (AIMS). Conversion of results into standard deviation (SD) units permitted defining a substantial difference as per Felson as > 0.30 SD units and a clinically indistinguishable difference as < or = 0.06 SD units. RESULTS: One hundred fifteen patients (97%) participated and complete data were available on 104 (87%). Compared to the early treatment group, the delayed group remained worse for both the pain and the physical disability outcomes over the additional 3 year followup. The difference in the RA global well being score became clinically indistinguishable for the early and delayed groups only after the 2 year post-trial assessment. The between-group differences were not explained by post-trial therapy with corticosteroids, other second-line agents, or nonsteroidal antiinflammatory drugs and analgesic preparations. CONCLUSION: These findings show that a delay in instituting therapy with second-line agents, even a 9 month delay in instituting a moderately powerful second-line agent such as HCQ, has significant effects on longterm patient outcome, and provides strong evidence in support of early therapy in RA.

Schieir O, Thombs BD, Hudson M, Taillefer S, Steele R, Berkson L, Bertrand C, Couture F, Fitzcharles MA, Gagné M, Garfield B, Gutkowski A, Kang H, Kapusta M, Ligier S, Mathieu JP, Ménard H, Mercille S, Starr M, Stein M, Zummer M, Baron M. · SMBD-Jewish General Hospital, 4333 Cote Ste Catherine Road, Montreal, Quebec H3T 1E4. · J Rheumatol. · Pubmed #19132790 No free full text.

Abstract: OBJECTIVE: To assess the longitudinal relationships, including directionality, among chronic pain, symptoms of depression, and disease activity in patients with early inflammatory arthritis (EIA). METHODS: One hundred eighty patients with EIA completed an examination, including swollen joint count, and were administered the Center for Epidemiological Studies Depression Scale (CES-D) and the McGill Pain Questionnaire (MPQ) at 2 timepoints 6 months apart. Cross-lagged panel path analysis was used to simultaneously assess concurrent and longitudinal relationships among pain, symptoms of depression, and number of swollen joints. RESULTS: Pain, symptoms of depression, and number of swollen joints decreased over time (p < 0.001) and were prospectively linked to pain, symptoms of depression, and number of swollen joints, respectively, at 6 months. Symptoms of depression and pain were correlated with each other at baseline (0.47) and at 6-month followup assessments (0.28). Baseline symptoms of depression significantly predicted pain symptoms at 6 months (standardized regression coefficient = 0.28, p = 0.001), whereas pain and disease activity did not predict the course of any other variable after controlling for baseline values. CONCLUSION: Symptoms of depression predicted the trajectory of pain from baseline to 6 months. In addition, there were reciprocal/bidirectional associations between pain and symptoms of depression over time. More research is needed to better understand the relationship between pain and depressive symptoms and how to best manage patients with EIA who have high levels of both.

Fitzcharles MA, DaCosta D, Ware MA, Shir Y. · Montreal General Hospital Pain Centre, Montreal General Hospital, McGill University, Montreal, Quebec, Canada. · J Pain. · Pubmed #19070549 No free full text.

Abstract: We have examined the characteristics of the pain experience as well as barriers to optimal pain management in 60 patients with rheumatoid arthritis (RA) consecutively attending a specialist rheumatology practice. Pain was reported to be moderate to severe in 32 (53%) and mild to absent in 28 (47%). Sixty-five percent of all patients, including almost half of those with moderate to severe pain, reported satisfaction with current pain control. The average number of barriers to pain management for individual patients was 2.6 +/- 1.5, with 33 patients (55%) reporting 3 or more barriers. Specific barriers included concern about side effects of medications in 80%, dislike for "too many pills" in 63%, concern about drug interactions in 57%, fear of addiction in 35%, and fear of masking disease in 27% of the patients. More barriers were significantly associated with higher pain level (r = .33, P = .011) and pain intensity on a visual analogue scale (r = .29, P = .024). Other than the regular use of nonsteroidal anti-inflammatory drugs in 37% of the patients and acetaminophen in 37%, analgesics or other modalities to reduce pain were seldom used. PERSPECTIVE: Moderate to severe pain was present in over half of patients with RA with many reporting the presence of considerable barriers to pain control. These barriers likely contribute to sub optimal pain management. RA patients tolerate pain and use limited mechanisms to deal with the symptom of pain.

Baron M, Schieir O, Hudson M, Steele R, Kolahi S, Berkson L, Couture F, Fitzcharles MA, Gagné M, Garfield B, Gutkowski A, Kang H, Kapusta M, Ligier S, Mathieu JP, Ménard H, Starr M, Stein M, Zummer M. · McGill University, Montreal, Quebec, Canada. · Arthritis Rheum. · Pubmed #18311751 links to  free full text

Abstract: OBJECTIVE: To assess the clinimetric properties of a new health-related quality of life (HRQOL) instrument, the World Health Organization Disability Assessment Schedule II (WHODAS II), in patients with early inflammatory arthritis. METHODS: Internal consistency as well as criterion, construct, and discriminative validity of the WHODAS II were assessed in 172 patients with early inflammatory arthritis who completed the WHODAS II, the Medical Outcomes Study Short Form 36 (SF-36), and other measures of disease severity, functioning, pain, depression, and resource use. Test-retest reliability of the WHODAS II was assessed by having a subset of 20 patients complete the WHODAS II a second time, 1 week after the first assessment. RESULTS: The WHODAS II had high internal consistency (Cronbach's alpha = 0.96 for patients working or in school and 0.93 for patients not working or in school). Test-retest intraclass correlation coefficients of the WHODAS II total score and subscales ranged from 0.82-0.96. The WHODAS II total score was strongly correlated with the SF-36 physical component score (Kendall's tau-b 0.51, P < 0.001) and moderately correlated with the SF-36 mental component score (tau-b 0.43, P < 0.001). WHODAS II correlations with disease outcomes ranged from Kendall's tau-b 0.15-0.55. The WHODAS II significantly differentiated between every aspect of disease severity assessed with the exception of measures of health resource use. CONCLUSION: The WHODAS II is a valid and reliable measure of HRQOL in cross-sectional studies of patients with early inflammatory arthritis. Research is still required to investigate potential item redundancy and determine its usefulness in longitudinal studies.

Poole AR, Ionescu M, Fitzcharles MA, Billinghurst RC. · Joint Diseases Laboratory, Shriners Hospitals for Children, Montreal, Quebec, Canada. · J Immunol Methods. · Pubmed #15637808 No free full text.

Abstract: A monoclonal antibody has been developed which recognizes a neoepitope in type II collagen which is generated by the intrahelical cleavage of collagenases. Antibody reactivity is directed at the carboxyl-terminus of the TCA or 3/4 piece of the degraded alpha1(II) chain. Reactivity is dependent upon hydroxylation of proline. Evidence is provided suggesting that epitope binding involves the recognition of a conformational neoepitope. Using an ELISA, we show that this neoepitope can be detected in the urines and sera of nonarthritic persons and patients with rheumatoid arthritis (RA). An increased content is observed in the sera and urines of patients. The assay may be of value in studying cartilage type II degradation both in vitro and in vivo such as in those with arthritis.

Panopalis P, Stone M, Brassard A, Fitzcharles MA. · Department of Medicine, McGill University, Montreal, Quebec H3G 1A4, Canada. · J Rheumatol. · Pubmed #15290752 No free full text.

This publication has no abstract.

Louis M, Rauch J, Armstrong M, Fitzcharles MA. · Division of Rheumatology, McGill University Health Centre at Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4. · J Rheumatol. · Pubmed #14719194 No free full text.

Abstract: OBJECTIVE: To determine the frequency and correlates of autoantibody formation in patients with rheumatic diseases treated with infliximab in a routine clinical setting. METHODS: All patients receiving at least 5 infusions of infliximab, and with anticipated continuation, were prospectively evaluated for the development of the following antibodies: antinuclear antibody (ANA), anti-DNA, anti-Sm, anti-RNP, anti-SSA and anti-SSB. Correlates with pharmacologic treatments, response to infliximab, and adverse events were assessed. RESULTS: Seventy-six percent of 42 patients receiving prolonged treatment with infliximab developed new autoantibodies, and these persisted in 57%. The most common new autoantibody was ANA in 45%, followed by anti-DNA in 33%, anti-Sm in 31%, and anti-RNP in 29%. New autoantibody formation was associated with both a greater number of infusions (p = 0.015) and a higher total dose of infliximab infused (p = 0.047). No other treatment, disease characteristic, or loss of efficacy to infliximab discriminated between those developing antibodies compared to those without new antibody formation. No patient developed clinical signs of a new connective tissue disease. CONCLUSION: Autoantibody formation is seen commonly in patients receiving prolonged treatment with infliximab. Concomitant immunosuppressive treatments did not preclude the formation of antibodies. The clinical significance of antibody formation remains to be determined.

Fitzcharles MA, Clayton D, Ménard HA. · Division of Rheumatology, McGill University, Montreal, Quebec, Canada. · J Rheumatol. · Pubmed #12465146 No free full text.

Abstract: OBJECTIVE: To audit a first clinical experience of treating rheumatic disease patients with infliximab in the setting of an academic tertiary care rheumatology practice. METHODS: The infusion history of patients referred to the McGill University Health Centre during the first 18 month period of a special access program for treatment with infliximab, a tumor necrosis factor-a antibody, was audited for disease characteristics, dosing schedule for infliximab, concomitant treatments, response rate, and side effect profile. RESULTS: Forty-one patients received a total of 300 infusions of infliximab over a period of 9 +/- 5 months (mean +/- standard deviation). Rheumatic disease indications were rheumatoid arthritis in 30, spondyloarthropathy in 6, psoriatic arthritis in 2, juvenile onset polyarthritis in 2, and scleroderma in one. Disease duration was 17 +/- 11 years. Concomitant treatment with steroids and methotrexate was present in 68% and 54%, respectively. Infliximab treatment was continued beyond 5 infusions or 22 weeks in 63%. Of the 26 patients continuing treatment, adjustment to dosing and/or interval schedule of infusions was made in 58%. The clinical response rate was moderately to greatly improved in 96%. Severe side effects considered directly related to the treatment were observed in 6 (15%) patients; less severe side effects, which did not preclude continuation of treatment but frequently required medical intervention, were noted in 93%. CONCLUSION: Infliximab is a valuable treatment for patients with resistant rheumatic diseases in the short term. Both the serious, and the frequent, more benign complication rate observed in this group of patients should alert physicians to be vigilant in the routine care of patients treated with infliximab.

Neville C, Fortin PR, Fitzcharles MA, Baron M, Abrahamowitz M, Du Berger R, Esdaile JM. · Clinical Epidemiology Unit, Arthritis Society of Canada Research Scholar, Quebec. · Arthritis Care Res. · Pubmed #10513496 No free full text.

Abstract: OBJECTIVE: To identify concerns and learning interests of patients with arthritis. METHODS: A questionnaire was developed, pilot tested, and then used to evaluate 197 patients with arthritis, including osteoarthritis (OA) (n = 41), rheumatoid arthritis (RA) (n = 57), back disease (n = 55), systemic lupus erythematosus (n = 27), and systemic sclerosis (SSc) (n = 17). Twenty concerns and 12 learning interests were rated. Questionnaires were also administered to assess physical disability (Health Assessment Questionnaire), psychological disability (Arthritis Impact Measurement Scales 2), and pain (visual analog scale). Participants addressed accessibility of health services, satisfaction with their physician, psychosocial needs, use of self-help groups, and behavioral strategies used to assist coping. Patients with RA, OA, and back disease, at both a community and a hospital center, were tested to assess whether concerns and learning interests differed based on site of treatment. Analytic methods included analysis of variance, factor analysis, and multiple linear regression. RESULTS: There were no differences in concerns or learning interests based on treatment site. Between diagnostic groups, patients with SSc were more interested in learning about self-help groups. The most frequently reported concern was worsening of the illness. The majority of respondents were interested in learning more about topics that were illness specific. The physician was chosen as the preferred source of information, and the preferred format was in writing. On factor analysis, the 20 concerns were reduced to 5 factors: psychological, coping, medication, social, and financial. Three factors were identified for learning interests: the illness, traditional health management topics, and nontraditional health management topics. Stepwise multiple linear regression revealed predictors for the 5 concern and 3 learning interest factors. The concerns were best predicted by self-reported disease severity, physical disability, and psychological distress, while learning interests were best predicted by self-reported disease severity, pain, and self-help group membership. CONCLUSION: Concerns and learning interests of persons with arthritis did not differ based on the center of treatment or the diagnosis, but can be predicted by the level of pain and simple measures of disability. Better understanding of the relationship between health status and patient-perceived needs will result in improved patient-centered care.