Disease-modifying drug retention rate according to patient age in patients with early rheumatoid arthritis: analysis of the ESPOIR cohort.

Physicians are sometimes hesitant to use disease-modifying antirheumatic drugs (DMARDs) in elderly patients with rheumatoid arthritis (RA), as they are deemed too fragile, although there are no sufficient scientific evidence. We aimed to compare DMARD treatment retention in early RA patients from the ESPOIR cohort, according to age upon inclusion. Overall, treatment retention was evaluated as the percentage of patients whose DMARDs were not stopped, with stratification by age group: < 50, 50-64, and > 65 years. Survival curves were measured using the Kaplan-Meier method. Of the entire ESPOIR cohort (n = 813), 7% were > 65 years old. Methotrexate (MTX) was used by 521 patients, and was the sole DMARD for 198 patients. MTX treatment retention appeared better in patients > 65 years old compared to < 50 years old [HR 0.45 (0.25; 0.81); p = 0.008, n = 195/198] with adjustment on sex, smoking, positive anti-cyclic citrullinated peptide antibodies, positive rheumatoid factor, body mass index, changes in DAS28 and corticosteroid treatment. The proportion of patients using etanercept (n = 111), and this drug's retention rate, did not differ according to patient age. The proportion of patients treated with adalimumab (n = 104) was significantly higher in patients < 50 years old (p = 0.003), and treatment retention was marginally better among younger patients [HR 1.68 (0.88; 3.22), p = 0.12]. Within the ESPOIR cohort, DMARD retention did not appear to differ according to age-except for better retention of MTX treatment in patients 50-64 years old, and of adalimumab in patients < 50 years old.

[Prospective assessment of a multidisciplinary meeting dedicated to inflammatory and vascular diseases during pregnancy]. / Évaluation prospective d'une réunion de concertation pluridisciplinaire dédiée aux pathologies inflammatoires et vasculaires lors de la grossesse : la RCP « PREGNANT ¼ au CHU de Bordeaux.

OBJECTIVES: The pluridisciplinary meeting "PREGNANT - Pregnancy and Auto-immunity, Nephropathy, Thrombophilic Disorders" at the university hospital of Bordeaux is dedicated to inflammatory and thrombophilic disorders during pregnancy. The objective of our study was to evaluate the quality of this meeting in terms of: compliance with the mandatory criteria, adequacy with standard care, homogeneity of care, becoming of proposals issued. METHODS: We conducted a prospective observational study including patients whose files were submitted to the meeting from January 2018 to June 2019. RESULTS: In all, 16 meeting were conducted with 152 cases presented. Sixty-two patients were pregnant and 90 were in preconception. The most common reasons for presentation were vasculo-placentary diseases (22.3%), systemic lupus (16.4%), venous thromboembolic diseases (15.1%) and chronic intervillositis of unknown etiology (9.8%). Other reasons were antiphospholipid antibody syndrome and repeated spontaneous miscarriages. The mandatory criteria for multidisciplinary meeting were met. For 89 cases (58.5%), the problem was dictated by recommendations. Decisions made were consistent with recommendations in 89.8% of cases. Among the 63 cases without any published recommendations (41.5%), there was some homogeneity of the proposals. In all, 92.8% of the proposals issued by the meeting were implemented. CONCLUSIONS: Multidisciplinary meeting "PREGNANT" has a prominent locoregional role in the management of patients with autoimmune, inflammatory or thrombophilic disorders in a pregnancy context.

Increased risk of mortality in systemic sclerosis-associated digital ulcers: a systematic review and meta-analysis.

BACKGROUND: Survival can be threatened in certain forms of systemic sclerosis (SSc) so clear prognostic factors are needed. OBJECTIVES: The aim of this meta-analysis was to assess the association between the presence of digital ulcers (DUs) and mortality in SSc. METHODS: We performed a systematic review and meta-analysis in the Pubmed and Scopus databases from the earliest records to May 2017. Two research strategies were performed: « systemic sclerosis ¼ and « digital ulcers ¼ (strategy A); « systemic sclerosis ¼ and « mortality ¼ (strategy B). The primary outcome was the mortality associated with the presence of DUs in patients with SSc. RESULTS: The literature search identified 1473 citations. Fifty-nine studies were examined for full text. Ten articles were included for the meta-analysis. SSc patients with DUs had an increased pooled mortality risk: RR = 1.53 (IC 95%: [1.23-1.90]). CONCLUSIONS: This meta-analysis revealed a higher mortality in SSc patients with associated DUs. Having DUs may be a predictive factor of developing organ involvement such as pulmonary or cardiovascular events that could be associated with poor survival. It suggests that early screening of DUs in SSc patients is important to identify patients most at risk of poor survival.

Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature.

We aimed to assess the efficacy of autologous haematopoietic stem cell transplantation (HSCT) for skin sclerosis (SSc) and lung function in SSc. We performed a systematic literature review in the PubMed and Scopus databases from the earliest records to March 2016. We assessed study quality using the Cochrane tool for randomized studies, the Newcastle-Ottawa Scale for controlled cohort studies and an 18-item quality-appraisal checklist for case series. The primary outcome was the improvement of skin thickening using the modified Rodnan Skin Score (mRSS). The secondary outcome was efficacy on lung function, using diffusing capacity of the lungs for carbon monoxide and forced vital capacity (FVC). The safety of the procedure was evaluated. The literature search identified 431 citations. There were 38 studies involving a total of 344 patients who fulfilled our inclusion criteria. No meta-analysis was performed due to a high heterogeneity. There was a significant improvement in mRSS in the majority of the reports (P < 0·05), and the results were sustained for up to 8 years after autologous HSCT. The randomized studies and the four cohort studies each showed a slight but statistically significant improvement in FVC at 1 or 2 years. The treatment-related mortality calculated by pooling patients of 35 studies (336 patients with a follow-up up to 146 months) was 8·3% after autologous HSCT and 1% in cyclophosphamide-treated groups. Despite heterogeneity among the studies, we determined that autologous HSCT significantly improved cutaneous fibrosis and slightly improved FVC. Safety of autologous HSCT is acceptable given the severity of the disease. This systematic review was registered on PROSPERO, number CRD42016027951.

[Relevance assessment of requests for antineutrophil cytoplasmic antibodies detection: Retrospective study led in Bordeaux Hospital, France]. / Évaluation de la pertinence des demandes d'anticorps anticytoplasme des polynucléaires neutrophiles : étude rétrospective menée au sein du centre hospitalier universitaire de Bordeaux.

INTRODUCTION: During year 2013, 5943 tests for antineutrophil cytoplasmic antibodies (ANCA) detection were performed in Bordeaux hospital, France. This seemed disproportionate, with regard to the low prevalence of ANCA-associated vasculitis (AAV). Our purpose was to evaluate the relevance of these requests. METHODS: Requests for detection of ANCA during 2013 were recorded, with their results. A sample of 501 requests was secondarily established. Relevance of requests was assessed independently by two reviewers. During year 2014, we developed strategies of information, in order to reduce the number of requests and increase their relevance. RESULTS: Only 17.8 % of the 5943 requests for detection of ANCA resulted in a positive test using indirect immunofluorescence (including 10.6 % of the requests with titles above 1/50). Using Luminex©, 9.7 % of the test of detection against antimyeloperoxidase or antiproteinase 3 antibodies were positive. Within the sample of 501 patients, only 28.7 % of the requests were relevant. A percentage of 40.2 of them weren't justified by a clinical affection typically associated with AAV. Exactly 15.9 of the requests were performed during systematic autoimmune screening. None of these requests could lead to the diagnosis of AAV. Combination of information procedures and use of a request form enabled a 19 % decrease of the number of requests. The percentage of requests without clinical justification also reduced from 40.2 % to 17.1 %. The reduction of the number of requests led to a 46,865 € saving. CONCLUSION: The majority of the requests for detection of ANCA was not relevant and could not lead to the diagnosis of AAV. Simple solutions enabled a partial but significant improvement of their relevance.

Opportunistic autoimmunity secondary to cancer immunotherapy (OASI): An emerging challenge.

With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists. Within irAEs, we propose to individualize the induced autoimmunity by the term "Opportunistic Autoimmunity Secondary to Cancer Immunotherapy" (OASI). The aims of this article are (1) to present the different available checkpoint inhibitors and the OASIs reported with these treatments and (2) to propose practical recommendations for diagnosis, pre-therapeutic assessment and management of OASIs. The need for predictive biomarkers of OASIs occurrence will also be discussed.

Influence of FCGR3A-V212F and TNFRSF1B-M196R genotypes in patients with rheumatoid arthritis treated with infliximab therapy.

OBJECTIVE: Anti-TNF-alpha therapies are widely used in rheumatoid arthritis (RA) patients. Despite their clearly proven efficacy, some discrepancies were observed in the treatment response with 40% of non-responder patients. The aim of this study is to determine whether two functional single-nucleotide polymorphisms, V212F in the FCGR3A, and M196R in the TNFRSF1B genes correlate with rheumatoid arthritis susceptibility and response to anti-TNF-alpha therapy. METHODS: The population study was composed of a French cohort of 78 RA patients and 70 healthy controls. Allele and genotype frequencies were compared between patients and controls, according to their response to infliximab therapy, using the American College of Rheumatology (ACR) response criteria. RESULTS: No association was found between these two SNPs and RA susceptibility. A significant correlation was found between 196R allele carriers and low response to infliximab therapy. CONCLUSION: This is the first report of a statistically significant association between the TNFRSF1B-M196R SNP and response to infliximab in a French cohort. Larger studies are needed to confirm the relevance of this association.

Anti-nuclear antibodies, anti-DNA and C4 complement evolution in rheumatoid arthritis and ankylosing spondylitis treated with TNF-alpha blockers.

OBJECTIVE: To investigate autoantibody induction in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in a cohort of French patients treated with TNF-alpha blockers. METHODS: We tested the serum of patients for antinuclear antibodies (ANA), anti-DNA antibodies and C4 complement at baseline, and for each infusion for infliximab, and at month 3, 6 and 12 for etanercept. We looked for all signs suggesting a drug-induced lupus. We tried to correlate ANA and anti-DNA development with various clinical data, especially the response to treatment. RESULTS: 229 patients were included in the study. 159 were treated with infliximab (98 RA and 61 AS) and 125 with etanercept (116 RA and 9 AS). In the infliximab group, 43.6% of RA patients and 27.1% of AS had significant levels of ANA at baseline. This proportion increased during the follow up to 73% in RA patients and 52% in AS patients. The proportion of patients positive for anti-DNA antibodies increased from 0% to 9.5% in RA group, and from 0% to 2% in AS group. In the etanercept group, 58.5% of these patients had significant levels of ANA at baseline; this proportion raised to 63.3% in patients previously treated with infliximab, and fell to 20.6% in the patients who never received TNF-alpha blockers. No significant variation of ANA, anti-DNA and C4 levels was observed in the etanercept group. Only three patients developed clinical manifestations (chilblain lupus) possibly related to these auto-antibodies, two with infliximab and one with etanercept. CONCLUSION: The ANA induction was only observed under infliximab therapy. Thus, ANA induction seems not to be a therapeutic class effect. This difference between infliximab and etanercept treatment may be the consequence of differential capacity of a monoclonal antibody and a soluble receptor in inducing apoptotic cell death of the cells expressing TNF on their membrane.

Role of anti-tumour necrosis factor-alpha therapeutic agents in the emergence of infections.

There is increasing interest concerning the possible impact of anti-tumour necrosis factor (TNF)-alpha therapeutic agents on the emergence of infections. However, these agents do not seem to increase the incidence of adverse infectious events significantly. Published observations concern mostly infections of the urinary and upper respiratory tracts that develop in the setting of co-morbidities, such as anterior or concomitant immunosuppressive treatment. Infliximab appears to increase the risk of tuberculosis, but this effect has not been observed with other anti-TNF-alpha agents. To better characterise the adverse infectious effects associated with these agents, physicians should be encouraged to notify the microbiological data relating to all cases.

Neuropathy resembling CIDP in patients receiving tumor necrosis factor-alpha blockers.

Tumor necrosis factor-alpha (TauNuFalpha) blockers are effective in the treatment of inflammatory arthritis but can induce autoimmune disorders including multiple sclerosis. Described are two patients who developed chronic inflammatory demyelinating polyneuropathy after initiation of anti-TNFalpha treatment.

Successful treatment of relapsing polychondritis with infliximab.

Relapsing polychondritis (RP) is a rare and potentially fatal autoimmune disease in which an inappropriate immune response destroys the cartilage of the ears, larynx and nose. Many therapeutic approaches have been reported. We describe the results obtained with infliximab in a patient with RP unresponsive to conventional therapy. This therapy could be a new weapon to treat refractory RP.

[Menstrual staphylococcal toxic shock is still a reality]. / Le choc toxique staphylococcique menstruel est toujours d'actualité.

INTRODUCTION: Staphylococcal toxic shock replies to precise clinical-biological criteria; but can be difficult to diagnose. Today, the nonmenstrual form of shock is the most frequent. The incidence of menstrual shock is low but their potential severity must be recalled. OBSERVATIONS: A young 14 year-old girl and a 33 year-old woman presented with menstrual shock that was treated successfully. A relapse in the form of staphylococcal scarlet fever occurred in the second patient. In both cases, the strain Staphylococcus aureus, which produces the TSST-1 toxin, had been identified. CONCLUSION: The possibility of the occurrence of a menstrual staphylococcal shock in the year 2002 must be known. The polymorphism of the clinical and biological manifestations must be underlined. The search for a toxin can be conducted in an appropriate centre.