BACKGROUND: ABP 501 was evaluated in a phase 3 single-arm, open-label extension (OLE) study to collect additional safety and efficacy data in patients with rheumatoid arthritis (RA). METHODS: Subjects completing the final visit in the parent phase 3 randomized, double-blind, controlled equivalence study comparing the efficacy and safety of the biosimilar ABP 501 with adalimumab reference product (RP) were enrolled in this open-label extension (OLE) study. All subjects received 40 mg ABP 501 every other week for 68 weeks. Key safety endpoints included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and anti-drug antibody (ADA) incidences. Efficacy endpoints included ACR20 (at least 20% improvement in American College of Rheumatology core set measurements from baseline) and Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP) change from baseline. RESULTS: Among 466/467 patients treated with ABP 501, 229 transitioned from the ABP 501 arm of the parent study (ABP 501/ABP 501) and 237 from the adalimumab RP arm (RP/ABP 501); 412/467 (88.2%) patients completed the study. The overall TEAE incidence was 63.7% (297/466); grade ≥ 3 TEAE incidence was 9.0% (42/466). The incidence of TEAEs leading to discontinuation of investigational product was 3.6% (17/466). The SAE incidence was 9.9% (46/466). Overall, 18.2% (85/466) of subjects developed binding ADAs and 6.9% (32/466) developed neutralizing ADAs in the OLE study. The ACR20 response rate was 73.3% (340/464 subjects) at OLE baseline, and 78.8% (327/415 subjects) at week 70 of the OLE study. The overall mean DAS28-CRP change from the parent study baseline was - 2.25 at the OLE study baseline (n = 440), - 2.36 at week 4 (n = 463), - 2.41 at week 24 (n = 450), - 2.55 at week 48 (n = 433), and - 2.60 at week 70 (n = 412). Efficacy was maintained throughout the study. CONCLUSIONS: Efficacy previously demonstrated in the parent study was maintained in this OLE study with no new safety findings. Long-term safety, immunogenicity, and efficacy were similar in the ABP 501/ABP 501 and RP/ABP 501 groups. The single switch from RP to ABP 501 did not impact immunogenicity. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02114931.

• MeSH
• adalimumab škodlivé účinky   terapeutické užití   MeSH
• antirevmatika škodlivé účinky   terapeutické užití   MeSH
• biosimilární léčivé přípravky škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• nazofaryngitida chemicky indukované   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• rozvrh dávkování léků MeSH
• senioři 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
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( ClinicalTrials.gov NCT01989468). METHODS: Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). RESULTS: Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. CONCLUSIONS: Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously. TRIAL REGISTRATION: ClinicalTrials.gov NCT01989468 . Registered 21 November 2013. EudraCT 2013-004002-25 . Registered 17 December 2013.

• MeSH
• autoaplikace MeSH
• bolesti hlavy chemicky indukované   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• injekce subkutánní MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• nazofaryngitida chemicky indukované   MeSH
• psoriatická artritida diagnóza   farmakoterapie   MeSH
• systémy cílené aplikace léků škodlivé účinky   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Daclizumab is a humanized monoclonal antibody against CD25 that modulates interleukin 2 signaling. The SELECT TRILOGY of clinical studies (SELECT/SELECTION/SELECTED) evaluated the safety and efficacy of daclizumab in patients with relapsing-remitting multiple sclerosis (RRMS). We report the long-term safety and efficacy of daclizumab 150 mg subcutaneous every 4 weeks in patients with RRMS in the SELECTED open-label extension study. METHODS: An interim intent-to-treat analysis of all enrolled patients was performed in January 2014 for this ongoing study. RESULTS: The SELECTED study enrolled 90% of patients who completed SELECTION. In the safety and efficacy analysis (N = 410), median treatment time in SELECTED was 25 months (range, <1-45). Adverse events (AEs) were reported in 76% of patients, serious AEs (SAEs) excluding MS relapse in 16%, and treatment discontinuation due to AEs including multiple sclerosis (MS) relapse in 12%. AEs were primarily of mild to moderate severity, and common AEs (≥10%), excluding MS relapse, were nasopharyngitis (12%) and upper respiratory tract infection (12%). Most commonly reported SAEs (in ≥3 patients), excluding MS relapses, were increased serum hepatic enzymes, pneumonia, ulcerative colitis, and urinary tract infection (<1% each). Incidences of AE groups of interest include cutaneous events (28%), cutaneous SAEs (2%), gastrointestinal SAEs (2%), hepatic SAEs, (1%) and malignancies (1%). The incidence of AEs, SAEs, and treatment-related study discontinuations did not increase over time and no deaths were reported. The adjusted annualized relapse rate (95% confidence interval (CI)) analyzed at 6-month intervals was 0.15 (0.10-0.22) for weeks 97-120 and 0.15 (0.10-0.21) for weeks 121-144. In year 3, the adjusted mean (95% CI) number of new/newly enlarging T2 hyperintense lesions was 1.26 (0.93-1.72) and the mean (median) annualized change in brain volume was -0.32% (-0.34%). CONCLUSIONS: The AE incidence did not increase with extension of therapy into year 3 in SELECTED; the safety profile was similar to that previously observed. The clinical efficacy of daclizumab was sustained over the 3 years comprising the SELECT TRILOGY, although potential selection bias cannot be excluded. TRIAL REGISTRATION: Clinicaltrials.gov NCT01051349; first registered January 15, 2010.

• MeSH
• alanintransaminasa účinky léků   MeSH
• analýza podle původního léčebného záměru MeSH
• aspartátaminotransferasy účinky léků   MeSH
• bezpečnost MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunoglobulin G aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• infekce dýchací soustavy chemicky indukované   MeSH
• infekce močového ústrojí chemicky indukované   MeSH
• injekce subkutánní MeSH
• kohortové studie MeSH
• léková dermatitida etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mozek účinky léků   MeSH
• následné studie MeSH
• nazofaryngitida chemicky indukované   MeSH
• pneumonie chemicky indukované   MeSH
• receptor interleukinu-2 - alfa-podjednotka aplikace a dávkování   terapeutické užití   MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• ulcerózní kolitida chemicky indukované   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací 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