Rheumatoid Arthritis: Tubach F

Gossec L, Tubach F, Dougados M, Ravaud P. · AP-HP, Rheumatology B Department, Cochin Hospital, 27 rue du faubourg St Jacques, Paris 5 University, Paris, France. · Am J Med Sci. · Pubmed #18030180 No free full text.

Abstract: BACKGROUND: International recommendations such as the CONSORT and International Conference on Harmonisation statements recognize patient adherence to prescribed treatment as an important aspect of a treatment's evaluation, but this issue is little assessed. OBJECTIVES: To evaluate how medication adherence was assessed and reported in recently published randomized controlled trials (RCTs). MATERIAL AND METHODS: All publications of RCTs assessing pharmacological treatments in 6 major chronic diseases published in high-impact-factor journals in 2003 and 2004 were selected from the Medline database. Two investigators analyzed how medication adherence was assessed and reported. RESULTS: A total of 192 publications were analyzed: 71 in HIV infection, 48 diabetes mellitus, 24 rheumatoid arthritis, 23 asthma, 15 hypertension, 7 osteoporosis, and 4 about 2 of these diseases. The assessment of medication adherence was documented in 69 (35.9%) publications, by counting pill intake in half of these. Results of adherence were reported in 64 (33.3%) publications. Adherence was reported as a quantitative measure: Proportion of the treatment prescribed in 27 articles and as a qualitative measure (adherent patient, yes/no) in 41 (in 4 reports both techniques were used). When reported, the median intake of prescribed medication was 93%, and the median proportion of "nonadherent" patients was 6.2%. CONCLUSIONS: There is important variability in the assessment and reporting of medication adherence in published RCTs of pharmacological treatments of selected chronic diseases, for a given disease and across diseases. Standardization is advisable to allow for comparisons among studies.

Tubach F, Wells GA, Ravaud P, Dougados M. · Département d'Epidémiologie, Biostatistique et Recherche Clinique, Groupe Hospitalier Bichat-Claude Bernard (AP-HP), INSERM U738, Faculté Xavier Bichat (Université Paris 7), Paris, France. · J Rheumatol. · Pubmed #16206363 No free full text.

Abstract: The importance of determining a minimal clinically important difference (MCID) and a low disease activity state (LDAS) as treatment targets in clinical trials no longer needs to be demonstrated. However, many methodological issues remain: whether these thresholds should be defined for each criterion or for composite criteria, whether there is a difference between the LDAS and patient acceptable symptom state (PASS), how to determine these thresholds (i.e., the wording of the questions and the statistical approach), and whether there are confounding factors in their evaluation. We consider these methodological issues and discuss their impact. Methods to determine the thresholds must be standardized, and recommendations could be endorsed by an OMERACT module. Threshold values for the MCID and LDAS should be determined according to data-driven and experts' opinions and approaches.

Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Bréban M, Pallot-Prades B, Pouplin S, Sacchi A, Chichemanian RM, Bretagne S, Emilie D, Lemann M, Lorthololary O, Mariette X, Anonymous00120. · Université Paris 7 Denis Diderot; INSERM U738; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bichat, Biostatistique et Recherche Clinique, Paris, France. · Arthritis Rheum. · Pubmed #19565495 No free full text.

Abstract: OBJECTIVE: Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence. METHODS: We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects. RESULTS: We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area. CONCLUSION: The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.

Denis B, Lefort A, Flipo RM, Tubach F, Lemann M, Ravaud P, Salmon D, Mariette X, Lortholary O, Anonymous00380. · Université Paris V, Hôpital Necker-Enfants Malades, Service des Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Paris, France. · Clin Microbiol Infect. · Pubmed #18076664 No free full text.

Abstract: This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.

Tubach F, Ravaud P, Salmon-Céron D, Petitpain N, Brocq O, Grados F, Guillaume JC, Leport J, Roudaut A, Solau-Gervais E, Lemann M, Mariette X, Lortholary O, Anonymous00158. · Université Paris 7, Faculté de Medecine, Paris, France. · Clin Infect Dis. · Pubmed #17051484 No free full text.

Abstract: BACKGROUND: Patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients receiving such therapy. METHODS: A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axée sur la Tolérance des Biothérapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-alpha antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-alpha antagonists was compared with the rate in France overall. RESULTS: We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40-69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-alpha antagonist treatment at onset of infection was 38.5 weeks (range, 3-73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-alpha antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy. CONCLUSIONS: L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti-TNF-alpha therapy. In patients receiving anti-TNF-alpha who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.