Safety and effectiveness of abatacept in systemic sclerosis: The EUSTAR experience.

OBJECTIVE: To analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc). METHODS: Retrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests. RESULTS: Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p<0.03 and p<0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p<0.05) and on morning stiffness at 6 and 12 months (p<0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p<0.05). No changes in lung or gastrointestinal involvement were found. CONCLUSIONS: ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care.

A regulatory role for CD72 expression on B cells in systemic lupus erythematosus.

BACKGROUND: B regulatory cells and their regulatory products/markers, such us semaphorin 3A (sema3A) and its receptor NP-1, FcγIIB, IL-10, and others, act at the very base of self-tolerance, maintenance, and prevention of autoimmune disease development. OBJECTIVES: The aim of the present study was to assess the involvement of CD72, a regulatory receptor on B cells, in systemic lupus erythematosus (SLE). In addition, the potential of soluble sema3A in enhancing the expression of CD72 on B cells of SLE patients was investigated. RESULTS: CD72 expression on activated B cells of SLE patients was significantly lower than that of normal controls. This lower expression of CD72 in SLE patients correlated inversely with SLE disease activity and was associated with lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. Co-culture of purified B cells from healthy controls with condition-media containing recombinant sema3A resulted in significant enhancement of CD72. Similar enhancement of CD72 on activated B cells from SLE patients, though significant, was still lower than in normal individuals. CONCLUSIONS: The lower expression of CD72 on activated B cells from SLE patients correlates with SLE disease activity, lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. The improvement of CD72 expression following the addition of soluble semaphorin 3A suggests that CD72 may be useful as a biomarker to be followed during the treatment of SLE.

Vaccination against influenza in patients with systemic sclerosis.

OBJECTIVES: To assess the efficacy and safety of the influenza virus vaccine in systemic sclerosis (SSc) patients compared to healthy controls. METHODS: Twenty-six SSc patients and 16 healthy controls were vaccinated with a trivalent influenza subunit vaccine (H1N1 A/Brisbane/59/2007(TGA 2008/81B) (H1N1), H3N2 A/Uruguay/716/2007 (A/Brisbane/10/2007-like, NIBSC8/124) (H3N2) and B B/Brisbane/60/2008 (TGA 2009/82/B) (B)). The subjects were evaluated on the day of vaccination and 6 weeks later. Disease activity was assessed by the Rodnan score, number of ulcers, number of tender and swollen joints, the presence of dyspnea, cough, dyspepsia and dysphagia, and patient (PDAI) and physician (PHDAI) disease activity evaluation by the visual activity score (VAS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. The humoral response was evaluated by haemagglutination inhibition (HI). RESULTS: At baseline, 62%, 15% and 88% of the SSc patients had protective levels against H1N1, H3N2 and B, respectively, versus 56%, 62% and 87% for controls. Six weeks later, the proportion of responders to H1N1 was significantly higher in the SSc patients (73%) compared to controls (37.5%) (p=0.0225). The proportion of responders to H3N2 and B was similar in both groups, and both had a significant increase in geometric mean titers for each antigen. A lower response to H1N1 was associated with interstitial lung disease, while patients on combination calcium channel blockers and iloprost therapy showed significantly better response to H1N1 and B antigens. Most underlying disease activity parameters remained unchanged. CONCLUSIONS: The influenza virus vaccine was safe and generated a satisfactory humoral response in SSc patients.

Fever of unknown origin: the role of 18F-FDG PET/CT.

UNLABELLED: Fever of unknown origin (FUO) is a challenging diagnostic problem. Timely identification and precise localization of the causing process are critical for appropriate patient management. The present prospective study evaluates the role of PET/CT using (18)F-FDG in the investigation of FUO. METHODS: A total of 48 consecutive patients (25 men, 23 women; age range, 24-82 y) with FUO underwent (18)F-FDG PET/CT scans. FUO was defined as a fever of more than 38.3 degrees C that lasted for more than 3 wk and failure to reach diagnosis after more than 1 wk of inpatient investigation. The performance of PET/CT for identifying the etiology of FUO was assessed. Final diagnosis was based on histopathology, microbiologic assays, or clinical and imaging follow-up. RESULTS: PET/CT detected suggestive foci of increased (18)F-FDG uptake in 27 patients. In 22 of these 27 positive studies (81%), PET/CT identified the underlying disease and diagnosed infection in 9 patients, an inflammatory process in 10 patients, and malignancy in 3 patients. (18)F-FDG PET/CT was negative in 21 patients. All these patients were diagnosed as having systemic nonfocal infection or drug-induced fever or showed spontaneous resolution of the febrile state with no further evidence of a localized inflammatory, infectious, or malignant process for a clinical follow-up period of 12-36 mo. CONCLUSION: (18)F-FDG PET/CT identified the underlying cause of the fever in 46% of the present study population and contributed to the diagnosis or exclusion of a focal pathologic etiology of the febrile state in 90% of patients. (18)F-FDG PET/CT has a high negative predictive value (100%) for assessment of FUO. If confirmed by further studies, (18)F-FDG PET/CT may be used in the future as an initial noninvasive diagnostic modality for assessment of this group of patients.