Secukinumab retention rate is greater in patients with psoriatic arthritis presenting with axial involvement.

Psoriatic arthritis (PsA) is an inflammatory disease characterized by peripheral and axial involvement. Biological disease-modifying antirheumatic drugs (bDMARDs) are the mainstream treatment for PsA and bDMARDs retention rate is a proxy for the drug's overall effectiveness. However, it is unclear whether IL-17 inhibitors can have a higher retention rate than tumor necrosis factor (TNF) inhibitors, in particular in axial or peripheral PsA. A real-life observational study was conducted on bDMARD naïve PsA patients initiating TNF inhibitors or secukinumab. Time-to-switch analysis was carried out with Kaplan-Meyer curves (log-rank test) truncated at 3 years (1095 days). Sub-analyses of Kaplan-Meyer curves between patients presenting with prevalent peripheral PsA or prevalent axial PsA were also conducted. Cox regression models were employed to describe predictors of treatment switch/swap. Data on 269 patients with PsA naïve to bDMARD starting either TNF inhibitors (n=220) or secukinumab (n=48) were retrieved. The overall treatment retention at 1 and 2 years was similar for secukinumab and TNF inhibitors (log-rank test p NS). We found a trend towards significance in the Kaplan-Meyer at 3 years in favor of secukinumab (log-rank test p 0.081). Predominant axial disease was significantly associated with a higher chance of drug survival in secukinumab users (adjusted hazard ratio 0.15, 95% confidence interval = 0.04-0.54) but not in TNF inhibitor users. In this real-life, single-center, study on bDMARD naïve PsA patients, axial involvement was associated with longer survival of secukinumab but not of TNF inhibitors. Drug retention of secukinumab and TNF inhibitors were similar in predominantly peripheral PsA.

Real-world experience of tocilizumab in rheumatoid arthritis: sub-analysis of data from the Italian biologics' register GISEA.

To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics' registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.

Plasmachemical Double Click Thiol-ene Reactions for Wet Electrical Barrier.

Click thiol-ene chemistry is demonstrated for the reaction of thiol containing molecules with surface alkene bonds during electrical discharge activation. This plasmachemical reaction mechanism is shown to be 2-fold for allyl mercaptan (an alkene and thiol group containing precursor), comprising self-cross-linked nanolayer deposition in tandem with interfacial cross-linking to the surface alkene bonds of a polyisoprene base layer. A synergistic multilayer structure is attained which displays high wet electrical barrier performance during immersion in water.

Study on the possible role of the -174G>C IL-6 promoter polymorphism in predicting response to rituximab in rheumatoid arthritis.

OBJECTIVE: Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. METHODS: The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. RESULTS: Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. CONCLUSION: IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.

[Sustained response to infliximab treatment in two cases of early rheumatoid arthritis that has been maintained after drug withdrawal]. / Due casi di artrite reumatoide trattati in fase precoce con infliximab con mantenimento dell'effetto dopo la sospensione del farmaco.

The authors report two cases of active seropositive rheumatoid arthritis who were treated in an early phase of the disease with infliximab plus methotrexate obtaining a clinical remission. The benefit was maintained after the discontinuation of the anti-TNF alpha inhibitor for adverse events, indicating that the early administration of the drug may be followed by a sustained remission.

[Chikungunya arthritis: report of 6 cases]. / Artropatia da Chikungunya: descrizione di 6 casi.

Chikungunya is an arboviral disease transmitted by Aedes mosquitoes. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia, that can persist for months. Chikungunya virus, a member of the genus Alphavirus, has recently caused a large outbreak on islands in the Indian Ocean and on the Indian subcontinent. The ongoing outbreak has involved more than 1.5 million patients, including travellers who have visited these areas. We describe our casistic of six travellers with Chikungunya arthropathy. All patients experienced fever and rash of short term during a travel in areas of epidemicity. All patients had peripheral poliarthralgias, which duration was >2 months in 4 cases (66%) and >6 months in 1 case (16%).

Scleroderma patients nailfold videocapillaroscopic patterns are associated with disease subset and disease severity.

OBJECTIVE: To evaluate in a large group of scleroderma patients, the association of nailfold videocapillaroscopic patterns with both demographic and clinical features. METHODS: One hundred and three Italian patients (91 women and 12 men, mean age 54.3 years, median disease duration 7 yrs, 68 with limited and 35 with diffuse subset of disease), consecutively enrolled for the study, underwent nailfold videocapillaroscopy; the microvascular alterations were classified into three different patterns, early, active and late. The nailfold videocapillaroscopic patterns were correlated with such numerous clinical features as sex, age, disease duration, disease subset, disease activity, haematochemical data, involvement of skin, heart, lung and peripheral vessels. RESULTS: Nailfold videocapillaroscopic patterns were significantly associated with disease subsets (P = 0.018). Severity of skin, lung, heart and peripheral vascular involvement progressively increased across nailfold videocapillaroscopic patterns, from early to late pattern (P < 0.001 for cutaneous and peripheral vascular involvement; P = 0.003 and 0.002 for lung and heart involvement, respectively) as well as homocysteine plasma levels (P = 0.02). Patients with late pattern showed an increased risk to have an active disease [OR (odds ratio) 3.50; 95% CI (confidence interval) 1.31-9.39], to present digital ulcers (OR 5.74; 95% CI 2.08-15.89) and moderate to severe skin (OR 5.28; 95% CI 1.93-14.19), heart (OR 5.75; 95% CI 2.04-16.21) and lung involvement (OR 4.41; 95% CI 1.63-11.92). CONCLUSIONS: Our study showed that scleroderma microangiopathy correlates with disease subset and severity of peripheral vascular, skin, heart and lung involvement; patients with late pattern showed an increased risk to have an active disease and to show a moderate/severe skin or visceral involvement compared to patients with early and active patterns. Therefore nailfold videocapillaroscopy, a simple, non-invasive and non-expensive investigation, is useful in staging scleroderma patients and also provides prognostic information.

Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features.

OBJECTIVE: Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. METHODS: Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. RESULTS: Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. CONCLUSIONS: Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns.

A case of ANCA-associated vasculitis with predominant involvement of central nervous system.

The authors present a peculiar case of a 53-year-old woman affected by ANCA-associated vasculitis with prevailing involvement of the central nervous system. Diagnosis was really difficult.

Cell contact-dependent PMN HLA-DR and CD69 membrane expression induced by autologous mono-lymphocytes and cell lines.

Polymorphonuclear granulocytes (PMN) are commonly considered short-lived cells playing an efficient role in primary host defense via phagocytosis and release of cytotoxic compounds and inflammatory cytokines. Purified PMN do not express HLA-DR and CD69 molecules on cell surface, but they can be induced to do so by co-culture with peripheral blood derived mono-lymphocytes. De novo cell-surface expression of HLA-DR was also induced in PMN by co-culture with cell lines of lymphoid phenotype, but not with cell lines of myeloid phenotype. CD69 expression was not induced by co-culture with any of the cell lines used in the present study. In addition, we have observed induction of HLA-DR surface expression on PMN by culture in presence of culture supernatant of one of the cell lines of lymphoid origin, RPMI-8866. Quantitative analysis of HLA-DR and CD69 expression in stimulated PMN allowed us to divide PMN donors in two main groups, one with low expression and the other with high expression of the two molecules. HLA-DR surface expression was not altered by treatment with CHX and BFA, and RT-PCR analysis of total RNA from resting and stimulated PMN with RPMI-8866 supernatant did not detect the presence of any specific HLA-DR and CIITA transcript. Flow-cytometry and fluorescence microscopy analysis of resting PMN revealed the presence of HLA-DR molecules localized in intracellular vesicular-tubular structures. These data show that a reservoir of HLA-DR molecules is stored in the cytoplasm of human resting PMN and can be released to reach cell surface by a mobilization mechanism induced by cell surface interactions with selected cell types and sometimes with molecules released in culture supernatants.

[Cyclosporin in atopic dermatitis]. / La ciclosporina nella dermatite atopica.

Cyclosporin A seems to became more and more important in the treatment of atopic dermatitis. Open, prospective study: 8 weeks of treatment and 6 months of follow-up in wash-out. 15 patients were selected (10 males and 5 females) with mean age of 35.5. The patients were suffering of atopic dermatitis non responder to preceding treatments, and free from any pathological conditions contra-indicating the use of cyclosporin A. Cyclosporin A was orally administered at the dosage of 5 mg/kg/day for 8 weeks. The patients used a diary with a score from 0 to 3 for the following symptoms: extensions of skin lesions, itch and sleeping sickness. Treatment with cyclosporin A induced a significant improvement of the parameters evaluated. No significant side effects were observed. No relapses were recorded during the six months of follow-up.

Mucosa-associated lymphoid tissue lymphoma of the salivary glands occurring in patients affected by Sjögren's syndrome: report of 6 cases.

OBJECTIVE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands occurring in 6 patients affected by primary Sjögren's syndrome is reported. METHODS: Clinical findings, histologic type, stage, treatment and outcome of the 6 patients have been revised. RESULTS: In all 6 cases the lymphoma was of the MALT type. Four patients had stage IE disease, 1 patient had stage IIE disease and 1 patient had stage IV disease. The patients received different treatments resulting in all cases in prolonged remission. After 7 years of complete remission 1 patient developed a diffuse large B-cell lymphoma. CONCLUSION: MALT lymphoma of the salivary glands is an indolent disease. Though the best therapy of this lymphoproliferative disorder remains to be established, prolonged remission has been obtained in our cases with different therapeutic approaches. We review the literature regarding the relationship between Sjögren's syndrome and MALT lymphomas and study the mechanisms which may be involved in the transformation from a lymphoepithelial lesion into a neoplastic disorder.

[Thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus. Clinical diagnosis and therapeutic strategies]. / Porpora trombotica trombocitopenica associata a lupus eritematoso sistemico. Inquadramento clinico-diagnostico e strategie terapeutiche.

The aim of our work is the focusing on some aspects about both the etiopathogenesis of thrombotic thrombocytopenic purpura and the therapeutic choices required to strongly reduce the mortality. Moreover the article reviews the association between thrombotic thrombocytopenic purpura and systemic lupus erythematosus. Thrombotic thrombocytopenic purpura is a rare and severe hematologic syndrome, first described in 1924, characterized by a clinical pentade: fever, microangiopathic anemia, thrombocytopenia, neurologic abnormalities and renal involvement. It is unknown if the endothelial damage represents the first lesion or if the platelet hyperaggregability precedes the vascular injury. Some data suggest a possible role of immune mechanisms in the development of the disease, that may be associated in some cases with autoimmune disorders. To our knowledge 31 cases of association between thrombotic thrombocytopenic purpura and systemic lupus erythematosus are reported in the English literature from 1970 today; the link between the two diseases is unclear. The authors review these cases with particular care to the diagnosis, that may be very difficult, and the therapy.

[Aspects of thrombophilia in Buerger's disease]. / Aspetti di trombofilia nel morbo di Buerger.

Buerger's disease or thromboangiitis obliterans is a disorder of unknown etiology which affects young heavy smokers, mainly of male sex; it is not clear why this disease afflicts only a little number of heavy smokers. Studies about genetic predisposition, autoimmune phenomena and platelet function have been performed in order to search additional etiologic factors without finding significant alterations. Recently some cases of Buerger's disease in association with hypercoagulable states have been described. The authors reported ten subjects affected by Buerger's disease, who have undergone to a clotting process evaluation. We have found 3 cases with fasting hyperhomocysteinemia in association with low level of plasma folate, 3 cases with high value of lipoprotein(a) (in 1 subject in association with IgG anticardiolipin antibody positivity), 1 case with IgM anticardiolipin antibody positivity. These findings, along with literature data, induce to hypothesize that hypercoagulable states may favour the clinical expression of Buerger's disease.