Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study.

OBJECTIVE: To evaluate the efficacy, immunogenicity and safety of the proposed biosimilar MSB11456 versus European Union (EU)-approved tocilizumab reference product in patients with rheumatoid arthritis (RA) in a multicentre, randomised, double-blind, multinational, parallel-group study (NCT04512001). METHODS: Adult patients with moderate-to-severe active RA and inadequate clinical response to ≥1 disease-modifying antirheumatic drug (synthetic or biologic) receiving methotrexate were randomised to receive 24 weekly subcutaneous 162 mg injections of either MSB11456 or EU-approved tocilizumab. Equivalence between treatments was considered if the 95% CI (European Medicines Agency)/90% CI (US Food and Drug Administration) for the difference in mean change from baseline to week 24 in Disease Activity Score-28 Joint Count with erythrocyte sedimentation rate (DAS28-ESR) between treatments was entirely within prespecified equivalence intervals (-0.6 to 0.6 and -0.6 to 0.5, respectively). At week 24, patients were rerandomised to continued treatment or MSB11456. Secondary efficacy endpoints to week 52, and safety and immunogenicity to week 55 were also evaluated. RESULTS: At week 24, the least squares mean difference in the change from baseline in DAS28-ESR between treatments was 0.01 (95% CI -0.19 to 0.22) in the 604 randomised patients. Similarity between treatments was shown for all other efficacy, safety and immunogenicity endpoints, including in patients who switched from EU-approved tocilizumab to MSB114466. CONCLUSIONS: Therapeutic equivalence was demonstrated for efficacy endpoints, and safety and immunogenicity analyses support the similarity of the two treatments. The results of this study strengthen the evidence that the proposed biosimilar MSB11456 and EU-approved tocilizumab exert similar clinical effects.

Blood serum levels of amino-terminal pro-C-type natriuretic peptide in patients with systemic sclerosis.

The aim of this pilot study was to examine the association of serum levels of amino-terminal fragment of pro-C-type natriuretic peptide (NT-proCNP), as a substitute measure of serum C-type natriuretic peptide (CNP), with clinical and laboratory findings in patients with systemic sclerosis (SSc). Serum NT-proCNP, soluble (s)E-and sP-selectin levels were examined using specific enzyme-linked immunosorbent assay in 30 patients with SSc and 30 healthy controls. We found no statistically significant difference in serum levels of NT-proCNP neither between patients with SSc and healthy controls nor between those treated with immunosuppressive agents and untreated patients. Nevertheless, in the investigated SSc group, serum NT-proCNP levels correlated with the concentrations of C-reactive protein (CRP) and the duration of the disease. Both sP- and sE-selectin levels were elevated in SSc patients when compared to healthy subjects. Also they did not correlate with the concentrations of NT-proCNP. The results of the study indicate that serum NT-proCNP level is likely secondary to existing inflammation. However, the magnitude of CNP action in SSc and its possible role in the pathogenesis of the disease remains to be elucidated.

Fucosylation of serum alpha1-acid glycoprotein in rheumatoid arthritis patients treated with infliximab.

To analyze fucosylation of alpha(1)-acid glycoprotein (AGP) and to identify relations between AGP fucosylation and clinical and biochemical indices of disease activity in patients with rheumatoid arthritis (RA) treated with monoclonal antitumor necrosis factor (TNF) antibody infliximab, we examined 22 patients with RA who underwent a 54-week treatment with infliximab according to ATTRACT protocol. Blood samples were collected at baseline and before every infusion of infliximab. AGP fucosylation was measured using lectin-binding enzyme-linked immunosorbent assay utilizing fucose-specific lectin Aleuria aurantia (AAL). Moreover, the clinical status/activity, erythrocyte sedimentation rate, serum C-reactive protein (CRP), antitrypsin, alpha(1)-antichymotrypsin, AGP reactivity with concanavalin A, serum C3 and C4 complement components, and serum concentrations of TNF and soluble TNF type 1 and type 2 receptors were determined. In most patients, the fucosylation of AGP decreased rapidly after first infusion of infliximab and remained low during the 54-week therapy (p < 0.001). The decrease in AGP affinity to AAL closely followed changes in clinical and laboratory activity of RA and correlated with pretreatment concentrations of CRP (r = 0.4986, p < 0.05) and TNF (r = 0.5181, p < 0.05). The fucosylation of AGP can be a part of a negative feedback loop regulating migration of inflammatory cells and collagenase-3 activity in RA. The decrease in AGP fucosylation accompanied by improvement in clinical and biochemical parameters of RA could possibly reflect reduced migration of inflammatory cells to inflamed joints and AGP-mediated inhibition of collagenase-3 as a response to infliximab treatment.

[Anticardiolipin antibodies and cardiac involvement in systemic lupus erythematosus]. / Przeciwciala antykardiolipinowe a zmiany w sercu u chorych na toczen ukladowy w badaniu echokardiograficznym.

UNLABELLED: Anticardiolipin antibodies (aCL) are present in 24-61% of patients (pts) with systemic lupus erythematosus (SLE). It is suggested that they may be associated with valvular abnormalities recognized on echocardiography (ECHO). To evaluate the relation of raised aCL and cardiac abnormalities we performed ECHO in 48 pts with SLE. ACL were estimated in all pts using enzyme-linked immunoabsorbent assay (ELISA), and positive result was found in 25 pts (52%), negative in 23 pts (48%). Abnormalities on ECHO were found in 18 pts in aCL(+) group vs 4 pts in aCL(-) group (68 vs 17% respectively; p < 0.01). Valvular abnormalities were present in 9 pts in aCL(+) group and in 4 ts in aCL(-) group (36 vs 17%; p = n.s.), pericardial effusion in 6 pts in aCL(+) group vs 0 pts in aCL(-) group (24 vs 0%; p < 0.05). CONCLUSION: We found association between raised aCL and general cardiac abnormalities on ECHO.