Carine Salliot

Indirect comparisons of the efficacy of biological antirheumatic agents in rheumatoid arthritis in patients with an inadequate response to conventional disease-modifying antirheumatic drugs or to an anti-tumour necrosis factor agent: a meta-analysis

Background The availability of increasing numbers of biological agents for the treatment of rheumatoid arthritis (RA) offers several therapeutic options. While all biologicals have proven effective in trials, very limited direct comparisons are available. The objective of the present work was to compare the efficacy of biologicals (anti-tumour necrosis factor (TNF) agents, rituximab, abatacept, tocilizumab) in patients with RA with active disease and (i) an inadequate response (IR) to methotrexate (IR-MTX), (ii) an IR to anti-TNF agents (IR-anti-TNFs) using indirect comparisons. Methods Randomised clinical trials were identified examining the efficacy of a biological agent in RA at 6 months in patients with an IR-MTX or with an IR-anti-TNF. To compare the relative efficacy of biologicals, adjusted indirect comparison meta-analytic methods to estimate the ORs of achieving a 50% improvement according to American College of Rheumatology criteria (ACR50) response at 6 months were used. Results A total of 18 published trials and 1 abstract were included in the analyses. In IR-MTX, anti-TNFs had the same probability of reaching an ACR50 compared to ‘non-anti-TNF biologicals’ taken together (OR 1.30, 95 % CI 0.91 to 1.86). However, when compared to specific biological agents, anti-TNFs demonstrated a higher probability of reaching an ACR50 than abatacept (OR 1.52, 95 % CI 1.0 to 2.28), but not in comparison to rituximab and tocilizumab. In IR-anti-TNF, rituximab demonstrated a higher probability of achieving an ACR50 than tocilizumab (OR 2.61, 95% CI 1.10 to 6.37), but no significant differences existed between rituximab, tocilizumab, abatacept and golimumab. Conclusions In a meta-analysis of randomised clinical trials of patients with IR-MTX, anti-TNFs demonstrated a higher probability of achieving an ACR50 response than abatacept. In IR-anti-TNF, no difference was found between rituximab, tocimizumab, abatacept and golimumab.

Hormonal replacement therapy may reduce the risk for RA in women with early arthritis who carry HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP: Results from the ESPOIR cohort.

Objective To assess the effect of reproductive factors, especially hormone replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04 alleles on the diagnosis of rheumatoid arthritis (RA) and the presence of anti-cyclic citrullinated peptide (CCP) antibodies in women included in the ESPOIR cohort (early arthritis cohort). Methods 568 patients were included in the analyses, which were performed using logistic regression. Results HRT reduced the risk of RA due to the HLA-DRB1 *01 and/or *04 alleles from OR 1.88 (95% CI 1.32 to 2.68, p<0.000) for HLA-DRB1 *01 and/or *04 alleles alone to OR 1.07 (95% CI 0.51 to 2.26, p=0.85) in women with HLA-DRB1 *01 and/or *04 alleles who received HRT. One explanation might be the protective effect of HRT on the presence of anti-CCP antibodies (OR 0.43, 95% CI 0.24 to 0.77, p<0.006). Other reproductive factors such as the number of pregnancies, menopause and age at menopause, age at menarche and a history of pregnancy with poor outcome were not associated with the diagnosis of RA and the presence of anti-CCP antibodies. Conclusion HRT may reduce the risk of RA due to HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP antibodies.

Diagnosis of peripheral psoriatic arthritis: Recommendations for clinical practice based on data from the literature and experts opinion

OBJECTIVEnTo propose French recommendations for the clinical, biological and radiological diagnosis of peripheral psoriatic arthritis (PsA) in daily practice based on data from the literature and expert opinion.nnnMETHODnThe strategy was the following: the choice of four questions, concerning this topic by the scientific committee according to the Delphi method, forming the basis of the recommendations. The Systematic literature research based on Medline, Cochrane and abstracts from the annual meetings of the French society of rheumatology (SFR), American college of rheumatology (ACR) and European ligue against rheumatism (EULAR). An experts committee of rheumatologists elaborated, validated specifying the strength and the degree of agreement of each recommendation.nnnRESULTSnThe questions selected were: (1) What clinical data should be collected to assist in the diagnosis of psoriatic arthritis? (2) What laboratory tests, immunological tests, and genetic tests should be performed to assist in the diagnosis of psoriatic arthritis? (3) What are the radiological investigations useful in the diagnosis of psoriatic arthritis? (4) What classification and/or diagnosis criteria can assist in the diagnosis of psoriatic arthritis? A literature search identified 1627 abstracts and 33 articles were included and analyzed. Four recommendations relative to the diagnosis were drafted and validated by a final vote of the experts committee.nnnCONCLUSIONnRecommendations concerning the diagnosis of PsA for daily practice were developed and validated on the basis of data from the literature and expert opinion. They should help to establish the diagnosis of PsA in daily practice.

Pharmacological treatment (biotherapy excluded) of peripheral psoriatic arthritis: Development of recommendations for clinical practice based on data from the literature and experts opinion

OBJECTIVESnTo develop recommendations about treatment (except anti-TNF agents) of psoriatic arthritis with peripheral joint involvement (PsA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed.nnnMETHODSnThe recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points of interest. Then, a literature task force looked for relevant publications in the following: Cochrane, Pubmed, and Ovid databases and abstracts from the French Society for Rheumatology, European League against Rheumatism and American College of Rheumatology. Based on the data from these publications, recommendations were drafted and then validated by a group of 68 experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts.nnnRESULTSnThe evidence extracted from 73 selected papers was presented to experts during interactive workshops. At the end of the workshops, the experts drafted six recommendations, which were then validated by a final vote including all participants. These six recommendations displayed various strength from B to D.nnnCONCLUSIONnThese recommendations should help to improve practice uniformity and, ultimately, to improve the management of PsA in France.

Prognosis and follow-up of psoriatic arthritis with peripheral joint involvement: Development of recommendations for clinical practice based on published evidence and expert opinion

OBJECTIVESnTo develop recommendations about prognosis and follow-up of psoriatic arthritis (PsA) with peripheral joint involvement in everyday clinical practice.nnnMETHODSnThe strategy was as following: (a) The choice of five questions, by the scientific committee according to the Delphi method, considered as a basis for the recommendations; (b) the Systematic Literature Research based on Medline, Cochrane and abstracts from the annual meetings of SFR, EULAR and ACR. An expert committee composed with 68 rheumatologists elaborated and validated the recommendations, specifying the strength and the degree of agreement for each of them.nnnRESULTSnThe questions selected were: (1) How can articular and cutaneous disease activity of PsA be assessed in usual clinical practice? (2) Which parameters are predictive for functional, radiological and fatal outcome in PsA? (3) Which clinical and biological parameters are useful for the follow-up of PsA? At which frequency? (4) Which X-rays are useful for the follow-up of PsA? At which frequency? (5) How can the response to treatments be assessed in PsA? The literature search identified 1181 abstracts and 123 articles were included and analyzed. Seven recommendations, whose strength ranged from B to D, were drafted and validated by a final vote of the expert committee.nnnCONCLUSIONnSeven recommendations about follow-up of patients with PsA for daily practice were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with PsA.

Precision and sources of variability in the assessment of rheumatoid arthritis erosions by HRpQCT

OBJECTIVESnTo assess the precision and the sources of variation due to repositioning of the manual measurement of erosions located on the metacarpophalangeal joints (MCP) with High-Resolution peripheral Quantitative Computed Tomography (HRpQCT) in rheumatoid arthritis (RA).nnnMETHODSnRA patients with at least one erosion on the 2nd, 3rd or 4th MCP on conventional radiographs were included. Two scans were performed the same day with repositioning. The main outcome was to calculate the short-term precision of the width, depth, and volume of erosions. Secondary outcomes were intra-operator and inter-operator precision, the least significant change, and the sources of variability of the measurement.nnnRESULTSnTwenty-nine patients were included, allowing analysis of 406 erosions from 0.9 to 3mm of diameter. Intraclass correlation coefficients (ICC) for the precision of the measurement of the axial width, axial depth, and volume after repositioning were 0.80, 0.96, and 0.99, respectively. RMS CV and RMS SD were 16%, 0.26mm; 17.5%, 0.32mm; and 19.7%, 0.93mm3, respectively. For intra-operator precision, ICCs were 0.92, 0.97, and 0.99 with RMS CV of 16%, 16.4%, and 18.7%, respectively. Inter-operator precision of the volume was 0.99 with RMS CV of 14%. Least significant change of width, depth, and volume were 0.3mm, 0.2mm, and 0.3mm3. There was no significant correlation with bone microarchitecture parameters.nnnCONCLUSIONnHRpQCT analysis is a reproducible method to characterize and measure erosions, without effect of the repositioning. However, we showed weak precision in manual measurement due to intra-operator variability.

Déterminants de la densité minérale osseuse volumétrique et sa relation avec les fractures ostéoporotiques dans la maladie de Parkinson idiopathique : étude DOPPA

Introduction L’osteoporose est une affection frequente. Son association avec la maladie de Parkinson idiopathique (MPI) a ete demontree. Le scanner peripherique a haute resolution (HRpQCT) evalue la structure osseuse en 3D. Objectifs Notre objectif principal etait d’etudier les facteurs associes a la densite minerale osseuse volumetrique (DMOv) et a la microarchitecture evaluees par HRpQCT au tibia et au radius dans la MPI. Patients et methodes Dans cette etude transversale monocentrique prospective, des patients atteints de MPI ont ete inclus avec recueil des caracteristiques de la maladie (Hoehn et Yahr, UPDRS III, dose cumulee de L-DOPA), du degre d’activite physique (International Physical Activity Questionnaire), et des antecedents fracturaires. Une biologie, une osteodensitometrie et une mesure de la force de poigne (FDP) ont ete realisees, ainsi qu’une acquisition des parametres osseux 3D (densite et microarchitecture) par HRxa0−xa0pQCT au tibia et au radius. Resultats Soixante-dix patients ont ete inclus (28xa0femmes, 42xa0hommes, duree moyenne d’evolution 7,6xa0ans). En analyse univariee, la DMOv n’etait pas correlee aux caracteristiques de la MPI. En revanche, le score de Hoehn et Yahr et l’UPDRS etaient significativement correles a des parametres microarchitecturauxxa0: le Mean Trabecular Area au tibia et le Tb. Th au tibia (pxa0 Discussion L’acquisition de la DMOv et des parametres microachitecturaux sur des sites peripheriques est faisable chez les patients parkinsoniens. Ces patients ont un risque plus eleve d’osteoporose que les sujets sains. Certains parametres etaient correles a des caracteristiques de la MPI, mais aussi a la force de la poigne, temoignant de la complexite de la fragilite osseuse dans cette affection. Conclusion Cette etude preliminaire a montre des correlations significatives entre les caracteristiques de la MPI et la microarchitecture osseuse, et apporte des bases d’evaluation par HR-pQCT dans cette pathologie.