Phase III randomized study of the proposed adalimumab biosimilar GP2017 in psoriasis: impact of multiple switches.

BACKGROUND: Adalimumab is used to treat several inflammatory diseases, including plaque psoriasis. GP2017 is a proposed adalimumab biosimilar. OBJECTIVES: To assess the impact of multiple switches between GP2017 and reference adalimumab (ref-ADMB) following the demonstration of equivalent efficacy and similar safety and immunogenicity, in adult patients with active, clinically stable, moderate-to-severe plaque psoriasis. METHODS: This 51-week double-blinded, phase III study randomly assigned patients to GP2017 (n = 231) or ref-ADMB (n = 234) 80 mg subcutaneously at week 0, then 40 mg biweekly from week 1. At week 17, patients were rerandomized to switch (n = 126) or continue (n = 253) treatment. The primary end point was patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16, with equivalence confirmed if the 95% confidence interval (CI) for the difference in PASI 75 between treatments was ± 18%. The key secondary end point was the change from baseline to week 16 in continuous PASI. Other end points were PASI over time; PASI 50, 75, 90 and100; pharmacokinetics; safety; tolerability and immunogenicity for the switched and continued treatment groups. RESULTS: Equivalent efficacy between GP2017 and ref-ADMB was confirmed for the primary (66·8% and 65·0%, respectively; 95% CI -7·46 to 11·15) and key secondary end points (-60·7% and -61·5%, respectively; 95% CI -3·15 to 4·84). PASI improved over time and was similar between treatment groups at week 16, and the switched and continued groups from weeks 17 to 51. There were no relevant safety or immunogenicity differences between GP2017 and ref-ADMB at week 16, or the switched and continued groups from weeks 17 to 51. No hypersensitivity to adalimumab was reported upon switching. CONCLUSIONS: Following the demonstration of GP2017 biosimilarity to ref-ADMB, switching up to four times between GP2017 and ref-ADMB had no detectable impact on efficacy, safety or immunogenicity.

Onychomycosis in patients with psoriasis--a multicentre study.

1-3% of human population is affected by psoriasis. Nail disorders are reported in 10-80% of patients with psoriasis. Nail deformations vary according to their degree of severity but are mainly represented by pitting, Beau's lines, hyperkeratosis, onycholysis, leuconychia or oil drops. Onychomycosis is a fungal infection of the nails, caused by dermatophytes, yeast and moulds. In this study, 228 patients with psoriasis aged between 18 and 72 were examined (48 - from Plovdiv, Bulgaria; 145 - from Pleven, Bulgaria and 35 - from Thessaloniki, Greece); 145 of them were male and 83 of them were female. The examination of the nail material was performed via direct microscopy with 20% KOH and nail samples plated out on Sabouraud agar methodology. The severity of the nail disorders was determined according to the Nail Psoriasis Severity Index (NAPSI). Positive mycological cultures were obtained from 62% of the patients with psoriasis (52%- Plovdiv, Bulgaria; 70%- Pleven, Bulgaria and 43%- Thessaloniki, Greece). In 67% of the cases, the infection was caused by dermatophytes, in 24% by yeast, in 6% by moulds and in 3% by a combination of causes. All patients with psoriasis were identified with high levels of NAPSI, whereas the ones with isolated Candida had even higher levels. Seventeen percentage of the patients have been treated with methotrexate, 6% have been diagnosed with diabetes and 22% have been reported with onychomycosis and tinea pedis within the family. An increased prevalence of onychomycosis among the patients with psoriasis was found. Dystrophic nails in psoriasis patients are more predisposed to fungal infections. The mycological examination of all psoriasis patients with nail deformations is considered obligatory because of the great number of psoriasis patients diagnosed with onychomycosis.

Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial.

AIMS: CF101 demonstrated a marked anti-inflammatory effect in Phase 2 studies conducted in patients with rheumatoid arthritis and dry eye syndrome. The aim of this study was to evaluate the safety and efficacy of CF101 for the treatment of patients with moderate to severe plaque-type psoriasis. MATERIALS AND METHODS: This was a phase 2, multicentre, randomized, double-blind, dose-ranging, placebo-controlled study. Seventy five patients with moderate to severe plaque-type psoriasis were enrolled, randomized and treated with CF101 (1, 2, or 4 mg) or placebo administered orally twice daily for 12 weeks. Safety and change from base line of Psoriasis Area and Severity Index (PASI) score and physician's global assessment (PGA) score over 12 weeks. RESULTS: In the 2 mg CF101-treated group, a progressive improvement in the mean change from baseline in the PASI score vs. placebo throughout the study period was observed, with a statistically significant difference on weeks 8 and 12 (P = 0.047; P = 0.031, respectively). In this group, 35.3% of the patients achieved PASI ≥ 50 response, and 23.5% of the patients achieved a PGA score of 0 or 1. CF101 was safe and well tolerated. CONCLUSIONS: CF101 was well tolerated and demonstrated clear evidence of efficacy in patients with moderate to severe plaque psoriasis.

Functional and metabolic studies on red blood cell sodium transport in chronic uremia.

Red blood cells from 7 out of 13 patients with chronic uremia were found to have increased intracellular concentrations of sodium associated with a reversible inhibition of ouabain-sensitive Na efflux when incubated in control plasma. Although mean Na-K-ATPase activity of RBC hemolysates was only moderately decreased (21.8 +/- 1.5 vs. 26.5 +/- 1.8 nmol Pi/mg protein/h), enzyme kinetics revealed a significant increase in KmATP values for this enzyme in uremic RBCs (1.01 +/- 0.1 vs. 0.58 +/- 0.03; p less than 0.001) which was closely correlated to serum creatinine concentration (r = 0.9034). While aerobic glycolysis was unaltered, an increase in glucose-6-phosphate dehydrogenase activity was observed, i.e. the enzyme initiating the pentose-phosphate cycle. In addition, intracellular ATP concentrations of uremic RBCs were significantly higher than ATP concentrations of control RBCs (2.13 +/- 0.22 vs. 1.32 +/- 0.06 mmol/l RBC; p less than 0.01). These data suggest that high intracellular concentrations of Na and ATP in uremic RBCs partially result from a competitive reversible inhibition of the transport ATPase by uremic toxins.