Rheumatoid Arthritis: Roux CH

Roux CH, Brocq O, Breuil V, Albert C, Euller-Ziegler L. · Rheumatology Department, University Hospital, Nice, France. · Rheumatology (Oxford). · Pubmed #17158212 links to  free full text

Abstract: OBJECTIVES: Anti-tumour necrosis factor (TNF)-alpha therapies are considered category B drugs for pregnancy. Although sometimes prescribed to women of reproductive age, data in humans are limited with regard to safety for a developing fetus. The objectives of the present article are to report experience of anti-TNF-alpha use in pregnancy, and review the international literature. METHODS: Since 1999 the present authors have used anti-TNF-alpha (infliximab, etanercept, adalimumab) to treat patients with various chronic rheumatic conditions. All patients were prospectively followed during their treatment time and data were systematically collected. RESULTS: In a group of 442 patients treated with anti-TNF, three women with RA unexpectedly became pregnant One treated with etanercept chose a therapeutic termination at two and a half months, despite of any ultrasound anomaly, and satisfactory fetal growth. The other two patients (one with adalimumab exposure and one with etanercept exposure) delivered healthy infants. The following perinatal complications were observed: prematurity, neonatal jaundice, neonatal urinary Escherichia coli infection and adrenal congenital hyperplasia of probable hereditary origin. CONCLUSIONS: To date, there is no evidence that TNF-alpha antagonists are associated with embryo toxicity, teratogenicity or increased pregnancy loss. However, caution should be taken when anti-TNF agents are used during pregnancy, as human experience is still extremely limited, particularly in patients with rheumatic diseases among whom there are several alarming reports. The potential risk should be balanced against the known risks associated with DMARDs and steroid therapy. Large registries will be necessary before firm conclusions can be drawn.

Brocq O, Millasseau E, Albert C, Grisot C, Flory P, Roux CH, Euller-Ziegler L. · Service de Rhumatologie, Hôpital L'Archet 1, 06200 CHU Nice, Université Nice, Sophia Antipolis, France. · Joint Bone Spine. · Pubmed #19362504 No free full text.

Abstract: OBJECTIVE: The objective of this study was to determine the time to relapse after tumor necrosis factor alpha (TNFalpha) antagonist discontinuation in patients with remission of rheumatoid arthritis (RA). METHODS: Among 304 patients taking TNFalpha antagonist therapy for RA, 21 achieved a remission and were taken off the TNFalpha antagonist. Remission was defined as DAS28<2.6 for at least 6 months without nonsteroidal inflammatory drugs or more than 5 mg of prednisone per day but with disease-modifying antirheumatic drug (DMARD) therapy if needed. The same TNFalpha antagonist was restarted in the event of a relapse (DAS28>3.2). RESULTS: The 21 patients had a mean age of 61 years, a mean disease duration of 11.3 years, and a mean remission duration at TNFalpha antagonist discontinuation of 19.2 months. The TNFalpha antagonist was infliximab in 2 patients, adalimumab in 5, and etanercept in 14; and 14 patients were taking a concomitant DMARD. The number of patients still in remission after TNFalpha antagonist discontinuation was 9/20 after 6 months and 5/20 after 12 months. Mean time to relapse was 14.7 weeks. While off TNFalpha antagonist therapy, 3 of the 5 relapse-free patients after 12 months were on DMARD therapy, compared to 11 of the 15 patients who relapsed. Compared to the 15 patients who relapsed, the 5 relapse-free patients had a longer time on TNFalpha antagonist therapy (56 months vs. 35 months, P=0.012) and a longer time in remission on TNFalpha antagonist therapy (35 months vs.14.5 months, P=0.04). The 15 patients who relapsed consistently achieved a remission after resuming TNFalpha antagonist therapy; the remission occurred within 2 months in 13 patients. CONCLUSION: TNFalpha antagonist discontinuation in patients in remission of RA was followed by a relapse within 12 months in 75% of cases. Relapsing patients responded well to resumption of the same TNFalpha antagonist.

Morvan J, Coste J, Roux CH, Euller-Ziegler L, Saraux A, Guillemin F. · School of Public Health, Nancy University, Nancy, France. · Ann Epidemiol. · Pubmed #18374278 No free full text.

Abstract: BACKGROUND: Two-phase surveys often are used to estimate prevalence, in particular when the disease is rare or the case ascertainment procedure difficult and/or costly. However, few authors of such surveys take into account the sensitivity error associated with the use of a screening procedure in the first phase and its imprecision in correcting the prevalence estimate and confidence interval. METHODS: Two examples of two-phase surveys of rheumatic diseases (hip and knee osteoarthritis, rheumatoid arthritis and spondyloarthropathies) are used to present methodological approaches to obtain corrected prevalence estimates. Two methods for assessing the accuracy of the screening procedure are described--two-phase pilot and case-control designs--that are best suited for frequent and rare diseases, respectively, and naive and corrected estimates of prevalence compared. RESULTS: When the sensitivity error is not taken into account, prevalence is underestimated, as is, especially, the width of its confidence interval. In our examples, the corrected confidence interval width increased up to 50% as compared with naïve one. CONCLUSIONS: The screening procedure accuracy should be thoroughly assessed in two-phase prevalence surveys and prevalence estimates and their confidence intervals corrected accordingly.

Brocq O, Roux CH, Albert C, Breuil V, Aknouche N, Ruitord S, Mousnier A, Euller-Ziegler L. · Service de Rhumatologie, CHU l'Archet 1, BP79, Nice Cedex 3, France. <> · Joint Bone Spine. · Pubmed #17368068 No free full text.

Abstract: OBJECTIVE: To evaluate TNFalpha antagonist continuation rates in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). METHODS: We retrospectively reviewed the charts of patients treated with etanercept, infliximab, or adalimumab at our teaching hospital. Drug continuation was evaluated using Kaplan-Meier survival curves. The logrank test was used to compare continuation rates. RESULTS: We identified 442 patients who were prescribed 571 TNFalpha antagonist treatments between August 1999 and June 2005. Among them, 304 had RA, 92 AS, and 46 PsA. In the RA group, continuation rates were high with etanercept (n=157; 87% after 12 months and 68% after 24 months) and adalimumab (n=43, 83% and 66%) but significantly lower with infliximab (n=104, 68% and 46%; P=0.0001 vs. etanercept and P=0.01 vs. adalimumab). In the AS group, in contrast, infliximab (n=53) showed significantly higher continuation rates (89% and 83%) than did etanercept (n=39; 76% after 12 months: P=0.03). Overall continuation rates were higher in AS than in RA (P=0.01). CONCLUSION: Continuation was better with etanercept than with infliximab in patients with RA, whereas the opposite was noted in patients with AS.

Roux CH, Brocq O, Leccia N, Giacchero D, Breuil V, Albert C, Lacour J, Perrin C, Euller-Ziegler L, Euler-Ziegler L. · Department of Rheumatology, University Hospital, Nice, France. · J Rheumatol. · Pubmed #17295430 No free full text.

Abstract: Reports of induction or exacerbation of psoriatic palmoplantaris pustulosis (PPPP) after anti-tumor necrosis factor-alpha (TNF-alpha) treatment are few. We describe 2 new cases of PPPP induced by infliximab. In 1999, a total of 442 patients in our department received anti-TNF-alpha treatment for a variety of chronic rheumatic conditions and were regularly followed. Medical records for 166 given infliximab were retrospectively reviewed for disease [rheumatoid arthritis (RA), spondylarthropathies (SpA) including psoriatic arthritis], disease duration, clinical characteristics, skin side-effects, and use of other potentially relevant medications. PPPP was observed in 2 patients treated with infliximab for symmetrical rheumatoid factor-positive RA; the patients had no personal or family history of psoriasis. In both cases, pustulosis appeared after several months of infliximab administration. There was no clinical, biological, or radiological evidence to support a diagnosis of psoriatic SpA. Both patients fulfilled ACR criteria for RA, and there was no reason to suspect previously unidentified psoriasis. Comorbid RA and psoriasis are unusual, and our patients exhibited a clear link between anti-TNF-alpha administration and cutaneous lesions, suggesting a direct effect in both cases. The 28 published cases of PPPP induced by anti-TNF-alpha treatment report lesions that tend towards pustulosis and palmoplantar localization. The mechanisms involved remain elusive. Disappearance of lesions in our second patient when switched to a soluble receptor suggests a molecule-specific side effect, while the literature describing variable reaction to switching anti-TNF agents, and/or their discontinuation and reintroduction, indicates otherwise. Given the rarity of this side effect, its elucidation will require systematic study.

Roux CH, Saraux A, Le Bihan E, Fardellone P, Guggenbuhl P, Fautrel B, Masson C, Chary-Valckenaere I, Cantagrel A, Juvin R, Flipo RM, Euller-Ziegler L, Coste J, Guillemin F. · Department of Rheumatology, University Hospital, Nice, France. · J Rheumatol. · Pubmed #17117490 No free full text.

Abstract: OBJECTIVE: To determine geographical variation in the prevalence of rheumatoid arthritis (RA) and spondyloarthropathies (SpA) in France. METHODS: The survey sample was drawn from 7 areas of France. Households were randomly selected using the national telephone directory, and an individual within each household was randomly chosen by the next-birthday method. All cases of suspected RA and SpA were confirmed by the patient's rheumatologist or by clinical examination. Standardized estimates of prevalence were compared between regions and groups of regions. RESULTS: In total 15,219 anonymous telephone numbers were selected. An average response rate of 64% led to a total of 9395 respondents included in the study. The highest regional rates of RA were observed in the south (range 0.59-0.66%), and the lowest in the north (range 0.14-0.24%), with a national rate of 0.31% (95% CI 0.18-0.48%). Regional heterogeneity was observed for SpA, with the highest rates in Bretagne (0.47%) and the Sud-Est (0.53%) and a national rate of 0.30% (95% CI 0.17-0.46%). CONCLUSION: This study is the largest of its kind conducted in France. It shows inter-regional variations, mainly in RA, with a higher prevalence in the south of the country. The many potential reasons for the heterogeneity observed, including genetic and environmental factors, warrant further research.

Roux CH, Brocq O, Breuil V, Albert C, Euller-Ziegler L. · Hospital l'Archet 1, Rheumatology Department, 242 Avenue de Saint Antoine de Ginestiere, 06200 Nice, France. · Rheumatology (Oxford). · Pubmed #16603583 links to  free full text

Abstract: OBJECTIVE: To assess the safety of anti-tumour necrosis factor (TNF)-alpha therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA) and concurrent chronic hepatitis B or C. METHODS: Records concerning 480 outpatients attending the Rheumatology Department of the University Hospital of Nice (France) for RA or SA were retrospectively reviewed for the duration of disease, treatment, serological status and biological data. RESULTS: Six relevant cases were identified: two of RA with chronic hepatitis B; one of SA with chronic hepatitis B and three of RA with chronic hepatitis C. Five patients had received etanercept and one infliximab; two had been given adalimumab after an unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B were also given lamivudine. In none of the cases had changes in serum aminotransferases or viral load been reported. CONCLUSION: The use of anti-TNF-alpha therapy (plus lamivudine in the presence of concurrent underlying hepatitis B viral infection) appeared to be safe in that it had no effect on serum aminotransferases and/or viral load. However, repeated monitoring is necessary throughout the treatment period.

Roux CH, Breuil V, Brocq O, Euller-Ziegler L. · Service de Rhumatologie du Professeur L. Euller-Ziegler, CHU Archet I de Nice, Hopital l'Archet 1, BP 3079 06202, Nice cedex 3, France. · Clin Rheumatol. · Pubmed #15940563 No free full text.

Abstract: We describe a case of IgD myeloma with amyloid and plasmocytic pleural localisations. At the onset of the disease it mimicked rheumatoid arthritis, which can be the first presentation of both AL amyloidosis and multiple myeloma. Pleural effusion can happen first in IgD myeloma, but our observation is of interest in that it confirms the very rare possibility of pleural amyloid and plasmocytic localisations devoid of pleural effusion.

Saraux A, Guillemin F, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, Cantagrel A, Chary-Valckenaere I, Euller-Ziegler L, Flipo RM, Juvin R, Behier JM, Fautrel B, Masson C, Coste J. · Rheumatology Unit, University Hospital, Brest-Cedex, France. · Ann Rheum Dis. · Pubmed #15817661 links to  free full text

Abstract: OBJECTIVE: To estimate the prevalence of spondyloarthropathies (SpAs) in France in a multiregional representative sample in the year 2001. METHODS: A two stage random sample was constituted in seven areas from the national telephone directory and the next birthday method in each household. Interviewers were patient-members of self help groups trained to administer telephone surveys using a validated questionnaire for detecting inflammatory joint disease. Quality of data collection was controlled periodically. SpA was confirmed by the patient's rheumatologist or by clinical examination. Prevalence estimates after probability sampling correction were standardised for age and sex (1999 national census). RESULTS: Among the 15 219 anonymous telephone numbers selected, 3.6% were places of work or secondary residences and were excluded. The phone interview participation rate ranged across regions from 55.1 to 69.9%. 3554 men and 5841 women were included in the study. Twenty nine cases of SpA were confirmed. All but one fulfilled ESSG criteria. Mean age was 47 years (range 21-78). The overall prevalence standardised for age and sex was 0.30% (95% confidence interval (CI) 0.17 to 0.46). Prevalence was similar in women (0.29% (95% CI 0.14 to 0.49)) and men (0.31 % (95% CI 0.12 to 0.60)). Geographical analysis by department clustering found no significant differences. The prevalence of SpA was as high as that of rheumatoid arthritis. CONCLUSION: Prevalence of SpA in France was 0.30% in 2001, with no difference between women and men. Ankylosing spondylitis and psoriatic arthritis were the most common SpA subsets.

Guillemin F, Saraux A, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, Cantagrel A, Chary-Valckenaere I, Euller-Ziegler L, Flipo RM, Juvin R, Behier JM, Fautrel B, Masson C, Coste J. · EA 3444 School of Public Health, Faculty of Medicine, University of Nancy, Nancy, France. · Ann Rheum Dis. · Pubmed #15800010 links to  free full text

Abstract: BACKGROUND: Prevalence estimates of rheumatoid arthritis (RA) vary across Europe. Recent estimates in southern European countries showed a lower prevalence than in northern countries. OBJECTIVES: To estimate the prevalence of RA in France in a multiregional representative sample in the year 2001. METHODS: A two stage random sample was constituted in seven areas (20 counties) from the national telephone directory of households and by the next birthday method in each household. Patient-interviewers, member of self help groups, were trained to administer telephone surveys using a validated questionnaire for case detection of inflammatory rheumatism, and conducted the survey under quality control. All suspected cases of RA were confirmed by their rheumatologist or by clinical examination. Prevalence estimates after probability sampling correction were standardised for age and sex (national census 1999). RESULTS: An average response rate of 64.7% (two stages combined) led to a total of 9395 respondents. Standardised prevalence was 0.31% (95% confidence interval 0.18 to 0.48) for RA, 0.51% in women and 0.09% in men, with a higher age-specific prevalence in the 65-74 year age band. A geographical analysis of county clustering showed significant variation across the country. CONCLUSION: This national multiregional cooperative study demonstrates the usefulness of working in association with patients of self help groups. It showed a similar prevalence of RA to that of the spondyloarthropathies estimated concomitantly during the survey. It provides a reliable basis for definition of population targets for healthcare delivery and drug treatments.

Roux CH, Brocq O, Albert C Breuil V, Euller-Ziegler L. · No affiliation provided · Joint Bone Spine. · Pubmed #15474402 No free full text.

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