Safety of Abatacept in Rheumatoid Arthritis With Serologic Evidence of Past or Present Hepatitis B Virus Infection.

OBJECTIVE: Rheumatoid arthritis (RA) with concomitant hepatitis B virus (HBV) infection represents a therapeutic challenge due to the risk of HBV reactivation under immunosuppressive treatment. To date there are few data coming from anecdotal case reports that concern HBV reactivation following treatment with abatacept. This observational retrospective study was aimed to assess the safety profile of abatacept in this particular clinical setting. METHODS: Eleven Italian rheumatologic centers provided data from patients with RA and positive HBV serology treated with intravenous abatacept. HBV markers and clinical and laboratory data were checked at followup visits every 3 months. RESULTS: In total, 72 patients were included in the study: 47 inactive carriers, 21 occult carriers, and 4 chronic active carriers for HBV. At baseline all of the patients had normal liver function tests and low or undetectable HBV DNA levels, except for those with chronic active hepatitis. Thirteen patients received prophylaxis with lamivudine, and 4 received treatment with adefovir or tenofovir. At the end of the 24-month followup period, 49 patients were being treated. Data from 316 followup visits showed that abatacept was safe. No patients experienced reactivation of hepatitis B. Treatment withdrawals (23 patients) were due to lack of efficacy, subject decision/lost at followup, or adverse events not related to HBV infection. CONCLUSION: Our study provides reassuring data about the safety profile of abatacept in RA with concomitant HBV infection without universal antiviral prophylaxis. Further prospective studies are needed to confirm these preliminary results.

Ultrasonography in the diagnosis and management of patients with inflammatory arthritides.

In primary care and internal medicine settings clinicians are often reluctant to take advantage of the resources that ultrasonography (US) offers as a diagnostic tool in the initial management of patients with inflammatory arthritis, despite the recognised importance of an accurate and timely diagnosis of rheumatoid arthritis (RA) and of early referral to ensure optimal patient management. Both grey-scale (GS) and power Doppler (PD) imaging have been extensively used in early detection of synovitis and bone erosions in patients with inflammatory arthritides. We reviewed the main data on the clinical use of US in the initial management of patients with inflammatory arthritis, focusing on RA diagnosis in patients with undifferentiated arthritis, prediction of disease severity, differential diagnoses and assessment of synovitis in children with juvenile idiopathic arthritis (JIA). The role of US in assessing treatment response and monitoring disease activity in clinical remission was also briefly evaluated. The reliability of US as a diagnostic tool in rheumatological diseases has greatly advanced in the last years and the use of this imaging technique, in association with conventional assessments such as physical examination and serological tests, should be considered more often also in primary care settings.

The arthritis-associated HLA-B*27:05 allele forms more cell surface B27 dimer and free heavy chain ligands for KIR3DL2 than HLA-B*27:09.

OBJECTIVES: HLA-B*27:05 is associated with AS whereas HLA-B*27:09 is not associated. We hypothesized that different interactions with KIR immune receptors could contribute to the difference in disease association between HLA-B*27:05 and HLAB*27:09. Thus, the objective of this study was to compare the formation of ß2m-free heavy chain (FHC) including B27 dimers (B272) by HLA-B*27:05 and HLA-B*27:09 and their binding to KIR immunoreceptors. METHODS: We studied the formation of HLA-B*27:05 and HLA-B*27:09 heterotrimers and FHC forms including dimers in vitro and in transfected cells. We investigated HLA-B*27:05 and HLA-B*27:09 binding to KIR3DL1, KIR3DL2 and LILRB2 by FACS staining with class I tetramers and by quantifying interactions with KIR3DL2CD3ε-reporter cells and KIR3DL2-expressing NK cells. We also measured KIR expression on peripheral blood NK and CD4 T cells from 18 HLA-B*27:05 AS patients, 8 HLA-B27 negative and 12 HLA-B*27:05+ and HLA-B*27:09+ healthy controls by FACS staining. RESULTS: HLA-B*27:09 formed less B272 and FHC than HLA-B*27:05. HLA-B*27:05-expressing cells stimulated KIR3DL2CD3ε-reporter T cells more effectively. Cells expressing HLA-B*27:05 promoted KIR3DL2+ NK cell survival more strongly than HLA-B*27:09. HLA-B*27:05 and HLA-B*27:09 dimer tetramers stained KIR3DL1, KIR3DL2 and LILRB2 equivalently. Increased proportions of NK and CD4 T cells expressed KIR3DL2 in HLA-B*27:05+ AS patients compared with HLA-B*27:05+, HLA-B*27:09+ and HLA-B27- healthy controls. CONCLUSION: Differences in the formation of FHC ligands for KIR3DL2 by HLA-B*27:05 and HLA-B*27:09 could contribute to the differential association of these alleles with AS.

Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests.

INTRODUCTION: Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. METHODS: Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7-±3.5-year follow-up. RESULTS: Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r=-0.57, P<0.0001) was observed; in addition, CFR was significantly reduced (2.21±0.38) in patients with WMA as compared to those without (2.94±0.60) (P<0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7-±3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests. CONCLUSIONS: A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases.

Joint and tendon involvement in systemic lupus erythematosus: an ultrasound study of hands and wrists in 108 patients.

OBJECTIVE: To estimate the prevalence of, and identify factors associated with, hand and wrist US alterations in a large cohort of SLE patients. METHODS: One hundred and eight consecutive SLE patients were recruited and classified according to arthropathy type and the musculoskeletal item of the British Isles Lupus Assessment Group (BILAG) 2004 score. US examinations were performed on hand and wrist flexor tendons, wrist extensor tendons, second and third MCP and wrist joints bilaterally using a multi-planar scanning technique. RESULTS: US examination showed joint involvement in 42/108 (38.8%) subjects, tendon involvement in 44/108 (40.7%) and both in 22/108 (20.3%). Patients with rhupus syndrome (n = 8) carried a higher incidence of inflammatory changes (87%) and erosions (87%) compared with the six with Jaccoud's arthropathy (50% and 17%, respectively) and the 94 with non-deforming X-ray non-erosive arthropathy (37% and 21%, respectively). Power Doppler signal was prevalent in patients scoring A (n = 4) or B (n = 9) on the musculoskeletal item of the BILAG 2004, and was significantly more frequent at the joint (92%) and tendon (54%) level than in the 26 patients scoring C (19%, P = 0.0007 and 15%, P = 0.016, respectively) and in the 69 scoring D (3%, P < 0.0001 and 3%, P < 0.0001). US changes in patients who scored C or D were more expressed at the tendon level (50% and 29%, respectively) than at the joint level (35% and 9%, respectively). CONCLUSION: The picture of musculoskeletal US in SLE depends on arthropathy subtype and disease activity. US examination could be a valid and reliable tool to monitor musculoskeletal features and therapeutic outcomes in SLE patients.