Rheumatoid Arthritis: Ramos-Remus C

Ramos-Remus C, Salcedo-Rocha AL, Prieto-Parra RE, Galvan-Villegas F. · Department of Rheumatology, Unidad de Investigación en Enfermedades Crónico-Degenerativas, Guadalajara, Mexico. · Baillieres Best Pract Res Clin Rheumatol. · Pubmed #11092796 No free full text.

Abstract: The prevalence and disability rate of rheumatic diseases are increasing. It seems that non-medical causes play an important role in the morbidity, disability and mortality of these patients. Efforts to reduce their impact are extremely important. Patient education is thought to be one way to limit disability in rheumatic diseases and to achieve an improvement in quality of life. In this chapter, we review the influence of non-medical causes of morbidity on disease outcome, some basic aspects of education and the evidence of the effectiveness of patient education in diseases such as ankylosing spondylitis, systemic lupus erythematosus, rheumatoid arthritis and fibromyalgia syndrome.

Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R, Anonymous00025. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Lancet. · Pubmed #18358926 No free full text.

Abstract: BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. FINDINGS: The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p<0.0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. INTERPRETATION: Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis. FUNDING: F Hoffmann-La Roche, Chugai Pharmaceutical.

Ramos-Remus C, Dorazco-Barragan G, Aceves-Avila FJ, Alcaraz-Lopez F, Fuentes-Ramirez F, Michel-Diaz J, Torres-Bugarin O, Ventura-Aguilar A, Zuñiga-González G. · Department of Rheumatology, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara. · Clin Exp Rheumatol. · Pubmed #12051400 No free full text.

Abstract: OBJECTIVES: This study investigated whether: (i) rheumatoid arthritis (RA) patients have more micronuclei (MN) than healthy controls; (ii) methotrexate (MTX) treated RA patients have more MN than those not using MTX, and (iii) folic acid supplementation decreases the number of MN in MTX treated patients. METHODS: MN assays were performed in oral mucosa sweeps of 50 consecutive MTX treated RA patients, 30 consecutive RA patients not receiving MTX and 39 healthy controls. MTX treated RA patients were then randomly placed in a cross-over design to receive folic acid supplementation, and MN assays were repeated after 6 weeks. RESULTS: The MTX-RA patients had a mean age of 46 +/- 10 yrs and a mean disease duration of 12 +/- 9 yrs; 80% were women. The MTX dose range was 8.7 +/- 1.5 mg/week and the mean duration of use was 16 +/- 18 months. In the non-MTX RA group, the mean age was 48 +/- 14 yrs, the mean disease duration was 13 +/- 9 yrs, and 87% were women. At baseline, the number of MN were significantly higher in RA patients as compared with controls (3.31 +/- 2.3 vs 0.8 +/- 0.8, p <0.001). No difference in MN numbers was observed between users and non-users of MTX. Folic acid supplementation did not decrease the MN number in the MTX treated RA patients. CONCLUSIONS: Genotoxicity, as assessed by the MN assay, is increased in RA patients. These results suggest that genotoxicity is associated with RA itself and not with MTX use. Folic acid supplementation had no effect on the number of MN.

Solano C, Martinez A, Becerril L, Vargas A, Figueroa J, Navarro C, Ramos-Remus C, Martinez-Lavin M. · National Institute of Cardiology, Mexico City, Mexico. · J Clin Rheumatol. · Pubmed #19342959 No free full text.

Abstract: BACKGROUND: It has been suggested that autonomic nervous system dysfunction may explain all of fibromyalgia (FM) multisystem features. Such proposal is based mostly on the results of diverse heart rate variability analyses. The Composite Autonomic Symptom Scale (COMPASS) is a different validated method to recognize dysautonomia. OBJECTIVES: The main objective of our study was to investigate symptoms of autonomic dysfunction in FM patients by means of COMPASS. A secondary objective was to define whether there is a correlation between COMPASS and Fibromyalgia Impact Questionnaire (FIQ) scores in FM patients. METHODS: Design, analytical cross-sectional study. Our study population included 3 different groups of women: 30 patients with FM, 30 patients with rheumatoid arthritis, and 30 women who considered themselves healthy. All participants filled out COMPASS and FIQ questionnaires. RESULTS: FM patients had significantly higher values in all COMPASS domains. COMPASS total score (54.6 +/- 20.9; mean +/- standard deviation) clearly differentiated FM patients from the other 2 groups (21.6 +/- 16.5 and 9.5 +/- 10.2, respectively). P < 0.0001. The majority of FM patients gave affirmative answers to questions related to orthostatic, digestive, sleep, sudomotor, or mucosal dysfunction. There was a significant correlation between COMPASS and FIQ scores (Spearman r = 0.5, P < 0.005). CONCLUSIONS: Patients with FM have multiple nonpain symptoms related to different expressions of autonomic dysfunction. There is a correlation between a questionnaire that measures FM severity (FIQ) and an autonomic dysfunction questionnaire (COMPASS). Such correlation suggests that autonomic dysfunction is inherent to FM.

Visser K, Katchamart W, Loza E, Martinez-Lopez JA, Salliot C, Trudeau J, Bombardier C, Carmona L, van der Heijde D, Bijlsma JW, Boumpas DT, Canhao H, Edwards CJ, Hamuryudan V, Kvien TK, Leeb BF, Martín-Mola EM, Mielants H, Müller-Ladner U, Murphy G, Østergaard M, Pereira IA, Ramos-Remus C, Valentini G, Zochling J, Dougados M. · Leiden University Medical Center, Department of Rheumatology, Leiden, The Netherlands. · Ann Rheum Dis. · Pubmed #19033291 links to  free full text

Abstract: OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

Mould-Quevedo J, Peláez-Ballestas I, Vázquez-Mellado J, Terán-Estrada L, Esquivel-Valerio J, Ventura-Ríos L, Aceves-Avila FJ, Bernard-Medina AG, Goycochea-Robles MV, Hernández-Garduño A, Burgos-Vargas R, Shumski C, Garza-Elizondo M, Ramos-Remus C, Espinoza-Villalpando J, Alvarez-Hernández E, Flores-Alvarado D, Rodríguez-Amado J, Casasola-Vargas J, Skinner-Taylor C, Anonymous00077. · Unidad de Investigación en Economía de la Salud, Instituto Mexicano del Seguro Social, México D.F., México. · Gac Med Mex. · Pubmed #18714591 No free full text.

Abstract: OBJECTIVE: To estimate the social costs of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout from the patient's perspective. METHODS: We carried out a cross-sectional analysis of the cost and resource utilization of 690 RA, AS, and gout patients from 10 medical centers and private facilities in five cities of Mexico. The information was obtained from the baseline of a dynamic cohort. We estimated out-of-pocket expenses, institutional direct costs, and direct medical costs. RESULTS: The mean (SD) annual out-of-pocket expense (USD) was $610.0 ($302.2) for RA, $578.6 ($220.5) for AS, and $245.3 ($124.0) for gout. Figures correspond to 15%, 9.6%, and 2.5% of the family income. They also represented 26.1%, 25.3%, and 24.4% of the total annual cost per RA, AS, and gout patients, respectively. The expected direct institutional patient/year costs were 1,724.2 for RA, $1,710.8 for AS, and $760.7 for gout. The total patient annual costs were $2,334.3 for RA, $2,289.4 for AS, and $1,006.1 for gout. Most out-of-pocket expenses were used to purchase drugs, pay for laboratory tests, imaging studies, and alternative therapies. CONCLUSIONS: From the patient's perspective, the cost of RA, AS, and gout represents 25% of direct medical costs. The cost of RA is higher than that for AS and gout.

Ramos-Remus C, Sierra-Jimenez G, Skeith K, Aceves-Avila FJ, Russell AS, Offer R, Olguin-Redes JE, Homik J, Sanchez L, Sanchez-Ortiz A, Navarro-Cano G. · Department of Rheumatology, Hospital de Especialidades del Centro Medico Nacional de Occidente, IMSS, Guadalajara, Mexico. · Clin Rheumatol. · Pubmed #17646901 No free full text.

Abstract: The mean age of rheumatoid arthritis (RA) onset is around 50 years as reported in several clinical trials involving Caucasian patients. However, clinical observations suggest that Mexican RA patients' disease is initiated at a younger age. The objective of the study was to assess whether the age of onset of RA is different in Mexican and in Canadian RA patients. Certified rheumatologists from Canada and Mexico directly interviewed consecutive RA patients attending their clinics regarding the date patients first noticed a swollen joint. None of the participant rheumatologists were aware of the primary aim of this exploratory study at the time of the interviews. Data was gathered from 161 Mexican (91% women) and 130 Canadian (77% women) RA patients collected by three rheumatologists in each country. Duration since disease onset was not different within countries (mean 95% confidence interval [CI] for differences -10 to 16 years, p = 0.12 for Canadians, and -6 to 10 years, p = 0.26, for Mexicans). However, there was a significant difference between the two countries. Mexicans patients on average developed RA almost 12 years younger than Canadians (95% CI for difference 9 to 15 years, p < 0.001). Frequency distribution showed that 35.5% of Canadians but only 4% of Mexicans had the onset of the disease after the age of 55 (all p < 0.001). It appears that RA begins at a much younger age in Mexican than Canadian patients. If this were confirmed after controlling for different confounders and biases, it would have important societal, economic, and therapeutic implications.

Aceves-Avila FJ, Delgadillo-Ruano MA, Ramos-Remus C, Gómez-Vargas A. · Departamento de Reumatología, Hospital de Especialidades del Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social. Guadalajara, Jalisco, México. · Reumatismo. · Pubmed #12089617 links to  free full text

Abstract: The rheumatic conditions found in New Spain during the sixteenth century were not different from those seen in Mexico in present times. We present the humoral conceptions on which medical theory was based in those times, and the contributions made by Alonso López de Hinojosos during his practice in the Hospital Real de San Josef de los Naturales, in Mexico City. Among them were the clinical distinction between gout and rheumatoid arthritis more than one hundred years before Sydenham, and the identification of arthritis and ocular involvement associated with a contagious disease more than three hundred years before Reiter. We conclude that the analysis of ancient medical traditions is an interesting and fruitful enterprise.

Suarez-Almazor ME, Belseck E, Homik J, Dorgan M, Ramos-Remus C. · Baylor College of Medicine, Houston, TX, USA. · Control Clin Trials. · Pubmed #11018564 No free full text.

Abstract: The objective of this study was to compare the performance of MEDLINE and EMBASE for the identification of articles regarding controlled clinical trials (CCTs) published in English and related to selected topics: rheumatoid arthritis (RA), osteoporosis (OP), and low back pain (LBP). MEDLINE and EMBASE were searched for literature published in 1988 and 1994. The initial selection of papers was then reviewed to confirm that the articles were about CCTs and to assess the quality of the studies. Selected journals were also hand searched to identify CCTs not retrieved by either database. Overall, 4111 different references were retrieved (2253 for RA, 978 for OP, and 880 for LBP); 3418 (83%) of the papers were in English. EMBASE retrieved 78% more references than MEDLINE (2895 versus 1625). Overall, 1217 (30%) of the papers were retrieved by both databases. Two hundred forty-three papers were about CCTs. Two-thirds of these were retrieved by both databases, and one-third by only one. An additional 16 CCTs not retrieved by either database were identified through hand searching. Taking these into account, EMBASE retrieved 16% more CCTs than MEDLINE (220 versus 188); the EMBASE search identified 85% of the CCTs compared to 73% by MEDLINE. No significant differences were observed in the mean quality scores and sample size of the CCTs missed by MEDLINE compared to those missed by EMBASE. Our findings suggest that the use of MEDLINE alone to identify CCTs is inadequate. The use of two or more databases and hand searching of selected journals are needed to perform a comprehensive search.

Vaile JH, Mathers DM, Ramos-Remus C, Russell AS. · Department of Medicine, University of Alberta, Edmonton, Canada. · J Rheumatol. · Pubmed #10332984 No free full text.

Abstract: OBJECTIVE: To assess the sensitivity to change of general quality of life indices in patients with rheumatic diseases, we assessed the performance of 4 instruments in patients with carpal tunnel syndrome (CTS) treated with local injection of corticosteroid. METHODS: We administered visual analog scales (VAS) incorporating measures of overall well being, discomfort, frequency of symptoms, and physical activity; 2 generic instruments [the Nottingham Health Profile (NHP), the Medical Outcomes Study 36 Item Short Form (SF-36)]; and a rheumatoid arthritis-specific instrument, the modified Health Assessment Questionnaire, at baseline and one month after injection. We assessed 30 patients. RESULTS: VAS were significantly better at determining improvement than the generic instruments or the arthritis specific instrument. For the generic scales, only the pain scales of NHP and SF-36 showed moderate or greater change using standardized response means. CONCLUSION: These results suggest that standard tools may not be sufficiently sensitive to show clinically significant change in this common rheumatological problem.

Gonzalez-Lopez L, Gamez-Nava JI, Jhangri GS, Ramos-Remus C, Russell AS, Suarez-Almazor ME. · Healthcare Quality and Outcomes Research Centre, Department of Public Health Sciences, University of Alberta, Edmonton, Canada. · J Rheumatol. · Pubmed #10090159 No free full text.

Abstract: OBJECTIVE: Palindromic rheumatism is characterized by attacks of acute arthritis of short duration. In the long term, a substantial proportion of patients will develop rheumatoid arthritis (RA) or other connective tissue diseases, but the determinants of subsequent chronic disease have not been adequately established. We identify clinical prognostic factors for the development of RA and other connective tissue diseases in patients with palindromic rheumatism in a retrospective cohort study. METHODS: The medical records of 4900 patients with arthritis referred from 1986 to 1996 to 3 rheumatologists at an academic center were reviewed. One hundred sixty patients were diagnosed as having palindromic rheumatism. After review, 127 complied with diagnostic criteria for palindromic rheumatism. Disease duration was estimated as time of first attack until the last consultation, or the development of RA or other connective tissue disease. Survival analysis including Cox regression was used to identify clinical variables associated with the risk of developing RA or other connective tissue disease, adjusting for varying disease duration. RESULTS: Sixty-five percent of the patients were female. Age at onset was 40+/-12 years. Mean disease duration was 6+/-6 years, and mean followup by the rheumatologists was 40+/-45 months. Joints more frequently affected were wrist, knee, and metacarpophalangeal. Forty-three patients (34%) subsequently developed a connective tissue disease including 36 (28%) RA, 3 (2%) systemic lupus erythematosus, and 4 (3%) other connective tissue diseases. In the final Cox regression model the hazard ratio for development of a connective tissue disease in the presence of a positive rheumatoid factor (RF) was 2.9 (p = 0.002), for proximal interphalangeal (PIP) joint involvement 2.4 (p = 0.02), for wrist involvement 2.5 (p = 0.05), for female sex 2.2 (p = 0.05), and for age at onset 1.03 (per year) (p = 0.001). Female patients with positive RF and involvement of the hands had an 8-fold risk of developing disease, compared with patients with one or fewer of these features. CONCLUSION: Positive RF and early involvement of the wrist and PIP joints predict the subsequent development of RA or other connective tissue disease in patients with palindromic rheumatism, and identify a group of patients at increased risk.