Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study.

BACKGROUND: Epstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas. Immunosuppressive drugs used to treat RA (conventional disease modifying drugs cDMARDs or biologics bDMARDs) could enhance the risk of developing LPD in RA patients. We have previously shown that long term treatment with Methotrexate and/or TNF alpha antagonists does not increase EBV load in RA. Our objective was to monitor the Epstein-Barr Virus load in RA patients treated with Abatacept (CTLA4 Ig), a T cell coactivation inhibitor, and Tocilizumab, an anti IL6 receptor antibody. METHODS: EBV load in the peripheral blood mononuclear cells (PBMCs) of 55 patients under Abatacept (in 34% associated with Methotrexate) and 35 patients under Tocilizumab (in 37% associated with Methotrexate) was monitored for durations ranging from 6 months to 3 years by real time PCR. The influences of treatment duration and disease activity score 28 (DAS28) index on EBV load were analyzed. RESULTS: Abatacept did not significantly modify EBV load over time. Tocilizumab significantly diminished EBV load over time. No patient (of 90) developed EBV associated lymphoma. CONCLUSION: Long term treatment with Abatacept or Tocilizumab does not increase EBV load in the PBMNCs of patients with RA.

Antinuclear Antibodies in Patients with Psoriatic Arthritis Treated or Not with Biologics.

BACKGROUND: With the emergence of biotherapies, accurate diagnosis in early arthritis is needed. At this time, there is no biological marker of psoriatic arthritis. OBJECTIVE: To test whether antinuclear antibodies (ANA) can be used as a diagnostic tool in psoriatic arthritis (PsA), we evaluated the prevalence of ANA in biologic-naïve PsA patients and in healthy blood donors. METHODS: 232 patients from the Rheumatology department, St Marguerite's Hospital, Marseilles, who fulfilled the CASPAR criteria for PsA, underwent clinical and laboratory investigations. Antinuclear antibodies (ANA), anti-extractable nuclear antigen antibodies (ENA), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) were assayed. Ninety-one healthy blood donors were also tested. RESULTS: Detection of ANA by indirect immunofluorescence was significantly more frequent in sera from PsA patients than those from controls at serum dilution of 1:100 (57% compared with 40%, Odds Ratio (OR) 1.98 (1.2-3.4) p<0.02) and 1:160 (52% compared with 24%, OR 3,7 (1.9-7.2) p<0.001). No patients had lupus specific autoantibodies, 15 % had RF (34/232), and 1.7 % had ACPA (4/232). CONCLUSIONS: Detection of ANA was more frequent in sera from PsA patients than in those from healthy controls. This suggests that ANA could be a diagnosis orientation tool in PsA. Nevertheless, the specificity of these antibodies still remains to be investigated.

Whole-Body (18) FDG-PET in an Arthritis Paraneoplastic Syndrome Revealed an Underlying Hematological Neoplasm.

We showed the first image of (18)FDG-PET, which leads to a diagnosis of lymphoma in an atypical polyarthritis. About 4% of patients with lymphoma or leukemia suffered from rheumatologic paraneoplastic symptoms like arthralgia and about 10% of the patients with rheumatologic or neurologic clinical symptoms develop a solid cancer or hematological neoplasm. (18)FDG-PET is an interesting exam to identify an underlying malignancy when a paraneoplastic syndrome is suspected; it can detect the primitive lesion and/or the metastasis lesions. The use of the (18)FDG-PET can help to detect earlier hematological neoplasm in cases of paraneoplastic syndrome without a determined cause and to treat more rapidly and specifically the patient.

Can we improve the diagnosis of spondyloarthritis in patients with uncertain diagnosis? The EchoSpA prospective multicenter French cohort.

UNLABELLED: Power Doppler ultrasound (PDUS) has proved to be a highly sensitive tool for assessing enthesitis in spondyloarthritis (SpA). In patients with a suspected SpA, diagnosis could be improved by detecting enthesitis with PDUS. OBJECTIVE: To evaluate the performance of PDUS for the diagnosis of SpA alone or combined with other clinical, laboratory and imaging findings in patients consulting for a suspected SpA. METHODS: Prospective, multicenter French cohort study (Boulogne-Billancourt, Brest, Caen, Grenoble, Marseille and Nancy). Outpatients consulting for symptoms suggestive of SpA (inflammatory back pain [IBP], arthritis or inflammatory arthralgia [IA], enthesitis or dactylitis [ED], HLA-B27 positive uveitis [B27+U], familiarity for SpA [Fam]) were recruited and followed up for at least 2 years. Sample size was set to 500 patients (for estimated prevalence of SpA of 30±5% after 2 years). At baseline, patients were submitted to standardized physical examination, pelvic X-ray, sacroiliac joints magnetic resonance imaging (MRI), HLA-B typing, and other tests judged useful for diagnosis. For each patient, a blinded PDUS examination of 14 enthesitic sites was performed at baseline and at years 1 and 2. Patients were planned to be followed during 5 years. The diagnosis of SpA ascertained by an experts' committee, blind to PDUS results, after at least 2 years of follow-up, with a revaluation of doubtful patients at 5 years will be used as gold standard for evaluating the diagnostic performance of PDUS and the best diagnostic procedure by combining PDUS, clinical symptoms and other tests. RESULTS: Between January 2005 and September 2007, 489 patients were included (96% of the target population). Nineteen patients (0.2%) retired their informed consensus or were lost to follow-up immediately after their inclusion. At baseline, mean age of the 470 remaining patients was 40 years, mean duration of symptoms was 6.1 years; 42% of them were HLA-B27+ and 63% were female. Primary inclusion criterion was IBP in 53%, IA in 27%, ED in 9%, B27+U in 8% and Fam in 4%. Follow-up is still ongoing. CONCLUSION: We have set up a unique diagnostic cohort which includes the entire spectrum of SpA manifestations. By using PDUS we expected to improve the diagnostic procedure of SpA.

Outcomes in recent-onset inflammatory polyarthritis differ according to initial titers, persistence over time, and specificity of the autoantibodies.

OBJECTIVE: To prospectively evaluate the predictive value of initial titers and subsequent variations of 3 rheumatoid arthritis­associated antibodies for outcomes at 30 months in patients with recent-onset polyarthritis. METHODS: IgM rheumatoid factor (RF), anti-Sa (citrullinated vimentin) antibodies, anti­ cyclic citrullinated peptide 2 (anti­CCP-2) antibodies, modified Health Assessment Questionnaire score, Disease Activity Score in 28 joints, and Sharp/van der Heijde radiologic scores were determined at baseline and at 18 and 30 months in a cohort of consecutive HLA­DR-typed treated patients with recent-onset polyarthritis aiming at remission. RESULTS: At inclusion, 113 (44.7%), 58 (22.9%), and 97 (38.3%) of 253 recent-onset polyarthritis patients were positive for RF, anti-Sa, and anti­CCP-2, respectively; at 30 months, 85 (33.6%), 31 (12.4%), and 100 (39.5%) patients were similarly positive. A low titer of any particular antibody was associated with higher risks for seroreversion. Similar to their persistent absence, reversion of RF and anti­CCP-2 was associated with low risks for severity. Patients who acquired RF or anti­CCP-2 after inclusion trended toward a poor prognosis. Relative to RF and anti­CCP-2 antibodies, only the presence of anti-Sa at inclusion, especially at higher titers and even when it subsequently disappeared, significantly predicted more rapid radiographic damage and lower remission rates at 30 months. CONCLUSION: In treated recent-onset polyarthritis, anti­CCP-2 prevalence is stable or increases slightly, whereas anti-Sa and RF frequently disappear. Subsequent reversion and conversion of RF and anti­CCP-2 blur the prognostic significance of initial RF and anti­CCP-2 positivity. Of the 3 antibodies, only anti-Sa, even if it disappears afterward, independently predicts severe outcomes.