Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
OBJECTIVE: The WEGENT trial and other short-term studies suggested that azathioprine or methotrexate could effectively maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission. Whether differences in relapse or adverse event rates would appear after discontinuation of those 2 maintenance regimens and longer follow-up remains unknown. METHODS: Long-term outcomes for the patients enrolled in the WEGENT trial were analyzed according to their randomization group. Parameters at trial entry were evaluated as potential prognostic factors for death, relapse or damage in multivariate models. RESULTS: Data were returned for 88.8% of the 126 original participants. Median [95% confidence interval] followup was 11.9 [11.3-12.5] years. For the azathioprine and methotrexate arms, respectively, the 10-year overall survival rates were 75.1% [64.8-86.9] and 79.9% [70.3-90.8] (P = 0.56), and relapse-free survival rates 26.3% [17.3-40.1] and 33.5% [23.5-47.7] (P = 0.29). No between-arm differences were observed for relapse, adverse events, damage, survival rates without severe side effects and survival rates without relapse and severe side effects. Considering only the 97 GPA patients, no between-arm survival differences were observed. Relapse-free survival was shorter for GPA than MPA patients but the multivariate analysis retained anti-PR3-ANCA-positivity, and not GPA, as being independently associated with relapse. CONCLUSION: This long-term analysis confirms that azathioprine and methotrexate are comparable options for maintaining GPA or MPA remission. Despite good overall survival, relapses, adverse events and damage remain matters of concern and further studies are needed to reduce them.
ISSN: 2326-5205

hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/file/Long-term%20outcomes%20of%20the%20WEGENT%20trial_accepted.pdf
DOI : 10.1002/art.39450

Éditeur(s) : HAL CCSD International Medical Press
Résumé : International audience
BACKGROUND: Psychiatric disorders are relatively common among HIV-infected patients. However, there are few studies about their potential risk factors. This analysis aimed to measure the incidence of severe psychiatric events (PE) among patients receiving combination antiretroviral therapy (cART) of the French APROCO-COPILOTE (ANRS CO8) cohort, and to identify the medical and socio-behavioural correlates of their first episode of depression, suicide or suicide attempt (D/S/SA). METHODS: APROCO-COPILOTE is a cohort of patients started on a protease inhibitor regimen between 1997 and 1999, with prospective medical standardized records and self-administered questionnaires collecting socio-demographic and socio-behavioural data. This analysis included all 11-year follow-up visits for 1,095 patients having completed baseline self-administered questionnaires. A proportional hazard Cox model was used to identify the correlates of a first D/S/SA event. RESULTS: The overall prevalence of severe PE remained low: 50 patients experienced 67 events (incidence rate [95% CI] =1.04 [0.82, 1.32] per 100 person-years). Depression (n=16), suicides (n=5) and suicide attempts (n=14) were the most frequently diagnosed PE (0.54 [0.39, 0.76] per 100 person-years) among 25 patients. Multivariate results showed that unemployment, unstable housing, detectable viral load and smoking more than 20 cigarettes/day were independently associated with D/S/SA. CONCLUSIONS: Although the incidence of severe PE remained relatively low among the patients of APROCO-COPILOTE cohort, this study's results underline a clinically important problem in HIV-infected patients receiving cART. Furthermore, our findings not only emphasize the importance of comprehensive care, especially for socially vulnerable patients, but may also help future studies designed to assess the effectiveness of interventions in reducing the risk of PE during cART.
ISSN: 1359-6535

hal-00875183
https://hal.archives-ouvertes.fr/hal-00875183
DOI : 10.3851/IMP2102
PUBMED : 22544079

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. METHODS: We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. RESULTS: Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. CONCLUSION: TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis.
ISSN: 1462-0324

hal-01155105
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01155105
DOI : 10.1093/rheumatology/kev129
PUBMED : 26001634

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. DESIGN: Prospective study of 1046 patients at 47 French clinical sites. METHODS: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. RESULTS: Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. CONCLUSIONS: In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.
ISSN: 0269-9370

hal-00875222
https://hal.archives-ouvertes.fr/hal-00875222
DOI : 10.1097/QAD.0b013e32834e8776
PUBMED : 22089377