OBJECTIVES: To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. METHODS: This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. RESULTS: 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). CONCLUSIONS: SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN. TRIAL REGISTRATION NUMBERS: NCT01895309, EudraCT 2012-005026-30.

• MeSH
• antirevmatika škodlivé účinky   imunologie   farmakokinetika   terapeutické užití   MeSH
• biosimilární léčivé přípravky škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• etanercept škodlivé účinky   imunologie   farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• protilátky krev   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři MeSH
• terapeutická ekvivalence MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Objective: To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA. Methods: In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated. Results: A total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively. Conclusion: Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN. Trial registration number: ClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30.

• MeSH
• antirevmatika terapeutické užití   MeSH
• biosimilární léčivé přípravky terapeutické užití   MeSH
• časové faktory MeSH
• dvojitá slepá metoda MeSH
• etanercept terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• progrese nemoci MeSH
• rentgendiagnostika metody   MeSH
• revmatoidní artritida diagnostické zobrazování   farmakoterapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

OBJECTIVE: Interleukin-20 (IL-20) is implicated in the pathogenesis of rheumatoid arthritis (RA). The efficacy, safety, and tolerability of NNC0109-0012, a selective anti-IL-20 recombinant human monoclonal antibody (mAb), were assessed in patients with active RA who had an inadequate response to methotrexate therapy. METHODS: Sixty-seven patients with RA were enrolled and randomized (2:1) to receive NNC0109-0012 (3 mg/kg per week, subcutaneously) or placebo in a phase IIa, double-blind, 12-week trial with a 13-week followup. The primary end point was change in the Disease Activity Score in 28 joints based on C-reactive protein level (DAS28-CRP) from baseline to week 12. RESULTS: In patients treated with NNC0109-0012, the primary end point, improvement in the DAS28-CRP at week 12, was achieved (estimated difference -0.88; P = 0.02), with significant improvement starting at week 1. A greater response was observed in seropositive patients (estimated difference -1.66; P < 0.001), which was sustained through 13 weeks of followup, whereas no improvement was noted in patients with seronegative RA. A significant proportion of patients with seropositive RA receiving NNC0109-0012, compared to those receiving placebo, achieved treatment responses according to the American College of Rheumatology 20% (ACR20) (59% versus 21%), ACR50 (48% versus 14%), and ACR70 (35% versus 0%) levels of improvement, and showed greater improvements in the Health Assessment Questionnaire disability index (P = 0.047). The most frequent adverse events reported with NNC0109-0012 were injection site reactions and infections (e.g., herpes, nasopharyngitis, respiratory, and urinary). No serious infections or discontinuations associated with NNC0109-0012 were observed. CONCLUSION: In this phase IIa trial, treatment with NNC0109-0012 (anti-IL-20 mAb) was effective in patients with seropositive RA as early as week 1, with further improvements to week 12. No safety or tolerability concerns were identified with weekly NNC0109-0012 administration.

• MeSH
• antirevmatika terapeutické užití   MeSH
• autoprotilátky imunologie   MeSH
• C-reaktivní protein imunologie   MeSH
• cyklické peptidy imunologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• herpes simplex chemicky indukované   MeSH
• infekce dýchací soustavy chemicky indukované   MeSH
• infekce močového ústrojí chemicky indukované   MeSH
• interleukiny antagonisté a inhibitory   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nazofaryngitida chemicky indukované   MeSH
• neutralizující protilátky terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   imunologie   MeSH
• revmatoidní faktor imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH