Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. Methods: In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634. Findings: Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42–13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25–13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14–4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. Interpretation: Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients

Publisher Copyright: © 2019 Novartis. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological SocietyAims: The aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL. Methods: A phase 1 study in healthy subjects with 6 devices to administer 2 mL injection volumes was conducted to evaluate the serum PK, safety and tolerability of secukinumab following single s.c. injection of 300 mg in the abdomen (either side) or in the thigh (either leg). Primary PK endpoints were maximum observed serum concentration and area under the serum concentration–time curve. The impact of device, site and side of injection on serum exposure was evaluated. In a phase 3 study in psoriasis patients, PK of secukinumab was evaluated following multiple s.c. injections of 300 mg by either 2 × 1-mL prefilled syringe or 1 × 2-mL prefilled syringe. Results: Mean serum concentration–time profiles for administration as 2 × 1 mL injections or as 1 × 2 mL injections were similar. With an injection volume of 2 mL, perceived injection pain was not different from 2 × 1 mL injections. A nonclinically significant difference in PK endpoints was observed between thigh and abdomen. Results with a 2 mL prefilled syringe in a 1-year phase 3 study in patients confirmed PK results observed in the phase 1 study. Conclusion: Collective evidence from both studies demonstrated that 2-mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticeable local reactions.Peer reviewe

Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials

peer reviewe

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different delivery systems in healthy volunteers and in psoriasis patients

Publisher Copyright: © 2019 Novartis. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological SocietyAims: The aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of secukinumab with different devices for subcutaneous (s.c.) administration of 2 mL. Methods: A phase 1 study in healthy subjects with 6 devices to administer 2 mL injection volumes was conducted to evaluate the serum PK, safety and tolerability of secukinumab following single s.c. injection of 300 mg in the abdomen (either side) or in the thigh (either leg). Primary PK endpoints were maximum observed serum concentration and area under the serum concentration–time curve. The impact of device, site and side of injection on serum exposure was evaluated. In a phase 3 study in psoriasis patients, PK of secukinumab was evaluated following multiple s.c. injections of 300 mg by either 2 × 1-mL prefilled syringe or 1 × 2-mL prefilled syringe. Results: Mean serum concentration–time profiles for administration as 2 × 1 mL injections or as 1 × 2 mL injections were similar. With an injection volume of 2 mL, perceived injection pain was not different from 2 × 1 mL injections. A nonclinically significant difference in PK endpoints was observed between thigh and abdomen. Results with a 2 mL prefilled syringe in a 1-year phase 3 study in patients confirmed PK results observed in the phase 1 study. Conclusion: Collective evidence from both studies demonstrated that 2-mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characteristics and were all well tolerated without noticeable local reactions.Peer reviewe

27519 Efficacy, pharmacokinetics, and tolerability of subcutaneous secukinumab injections with 2 mL prefilled syringes (300 mg) in adult subjects with moderate to severe plaque psoriasis

Sigurgeirsson B, Schäkel K, Hong C-H, et al. 27519 Efficacy, pharmacokinetics, and tolerability of subcutaneous secukinumab injections with 2 mL prefilled syringes (300 mg) in adult subjects with moderate to severe plaque psoriasis. Journal of the American Academy of Dermatology. 2021;85(3 (Suppl.): AB150

Efficacy, pharmacokinetics, and tolerability of subcutaneous secukinumab injections with 2 mL prefilled syringes (300 mg) in adult subjects with moderate to severe plaque psoriasis

Sigurgeirsson B, Schaekel K, Hong C-H, et al. Efficacy, pharmacokinetics, and tolerability of subcutaneous secukinumab injections with 2 mL prefilled syringes (300 mg) in adult subjects with moderate to severe plaque psoriasis. Journal of the American Academy of Dermatology. 2021;85(3, Suppl.):AB150

Comparison of pharmacokinetics, safety and tolerability of secukinumab administered subcutaneously using different 2 mL delivery systems in healthy volunteers and in psoriasis patients

Aims The aim of the study was to compare the pharmacokinetics, safety and tolerability of secukinumab with different devices for subcutaneous administration of 2 mL (i.e. 300 mg) secukinumab. Methods A phase 1 study in healthy subjects with six devices to administer 2 mL injection volumes was conducted to evaluate the serum pharmacokinetics (PK), safety and tolerability of secukinumab following s.c. injection of 300 mg in the abdomen or in the thigh at either the left or right side of the body. Primary PK endpoints were maximum observed concentration (Cmax), and areas under the curve (AUCinf and AUClast). The impact of site and side of injection on serum exposure was evaluated. In a phase 3 study in psoriasis patients, PK of secukinumab was evaluated following multiple s.c. injections of 300 mg by either 2 x 1 mL prefilled syringe or 1 x 2 mL prefilled syringe. Results Mean serum concentration-time profiles for administrations as 2 x 1mL injections or as 1 x 2 mL injections were similar. With an injection volume of 2 mL, perceived injection pain was not different from 2 x 1 mL injections. A non-clinically significant difference in PK endpoints was observed between thigh and abdomen. Results with a 2 mL prefilled syringe in a one year phase 3 study in patients confirmed PK results observed in the phase 1 study. Conclusions Collective evidence from a phase 1 study and phase 3 study demonstrated that 2 mL injections of secukinumab into the abdomen or thigh using different devices resulted in comparable PK characerisitics and were all well tolerated without noticable pain experiences

Efficacy, tolerability, patient usability, and satisfaction with a 2 mL pre-filled syringe containing secukinumab 300 mg in patients with moderate to severe plaque psoriasis: results from the phase 3 randomized, double-blind, placebo-controlled ALLURE study

Sigurgeirsson B, Schakel K, Hong C-H, et al. Efficacy, tolerability, patient usability, and satisfaction with a 2 mL pre-filled syringe containing secukinumab 300 mg in patients with moderate to severe plaque psoriasis: results from the phase 3 randomized, double-blind, placebo-controlled ALLURE study. Journal of Dermatological Treatment. 2022;33(3):1718-1726.Background Evidence shows good tolerability in patients for subcutaneous injection volumes up to 3 mL. Objectives We investigated efficacy, pharmacokinetics, and tolerability of secukinumab 300 mg/2 mL pre-filled syringe (PFS) in patients with moderate to severe plaque psoriasis. Methods ALLURE was a 52-week, multicenter, randomized (1:1:1), double-blind, placebo-controlled, parallel-group study. Co-primary endpoints were secukinumab Psoriasis Area Severity Index (PASI) 75 and Investigator's Global Assessment modified 2011 0/1 (IGA mod 2011 0 or 1) responses at week 12 versus placebo. Other endpoints included the Self-Injection Assessment Questionnaire (SIAQ), and the ability to follow the instructions for use (IFU). Results Overall, 214 patients were randomized. The secukinumab 300 mg/2 mL PFS showed superiority over placebo for both PASI 75 (88.9% versus 1.7%; p<.0001) and IGA mod 2011 0 or 1 (76.4% versus 1.4%; p<.0001) responses at week 12. All secondary efficacy endpoints were met. The SIAQ scores were similar across groups and improved similarly over 12 weeks. All patients completed critical steps in the IFU at week 1. Conclusions The secukinumab 300 mg/2 mL PFS groups showed superiority versus placebo, and it was a safe, effective, and convenient option for patients with psoriasis. NCT02748863

Secukinumab administration by a 2 mL autoinjector demonstrates high efficacy with comparable safety and tolerability in adult patients with plaque psoriasis: 16-week results from MATURE

Sigurgeirsson B, Browning J, Tyring S, et al. Secukinumab administration by a 2 mL autoinjector demonstrates high efficacy with comparable safety and tolerability in adult patients with plaque psoriasis: 16-week results from MATURE. Journal of the American Academy of Dermatology. 2021;85(3, Suppl.):AB154