SPIRIT-P1 and -P2 Trial Designs (PsA)1-4
SPIRIT-P1 (N=417) and -P2 (N=363) were phase 3, randomized, double-blind, placebo-controlled trials to evaluate the efficacy and safety of Taltz compared with placebo in patients with active psoriatic arthritis. Patients in SPIRIT-P1 were biologic-naive. Patients in SPIRIT-P2 were tumor necrosis factor inhibitor (TNFi)-experienced, having had an inadequate response and/or intolerance to 1 or 2 prior TNFis. In both trials, the primary efficacy endpoint was the proportion of patients achieving ACR20 response at week 24. All patients were ≥18 years of age and had ≥3 swollen and ≥3 tender joints. Patients were randomized to placebo or Taltz 80 mg every 2 or 4 weeks following a 160 mg starting dose. In SPIRIT-P1, an active reference arm of Humira® (adalimumab) 40 mg every 2 weeks was included. Patients in all study arms were allowed to continue taking stable background medications during the trial. Inadequate responders (as defined by blinded criteria of <20% improvement in tender and in swollen joint counts) at week 16 received rescue therapy and were analyzed as nonresponders after week 16 until the primary endpoint. After receiving rescue therapy, inadequate responders in the placebo and Humira arms were re-randomized to Taltz 80 mg every 2 or 4 weeks. Nonresponder imputation (NRI) methods were used for categorical efficacy analyses during the double-blind treatment period.
Humira® is a registered trademark of AbbVie Biotechnology Ltd.
References: 1. Taltz [package insert]. Indianapolis, IN: Lilly USA, LLC. 2. Mease PJ, van der Heijde D, Ritchlin CT, et al; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76:79-87. 3. Nash P, Kirkham B, Okada M, et al; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389:2317-2327. 4. Nash P, Kirkham B, Okada M, et al; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Supplementary material. Lancet. 2017;389:2317-2327.
SPIRIT-H2H Trial Design (PsA)1
SPIRIT-H2H (N=566) was a phase 4, randomized, open-label, blinded-assessor study evaluating the efficacy and safety of Taltz vs Humira® (adalimumab) in biologic-naive patients with active psoriatic arthritis and plaque psoriasis BSA ≥3%. The primary efficacy endpoint was the proportion of patients simultaneously achieving ACR50 and PASI 100 at week 24. All patients were ≥18 years of age and had ≥3 swollen and ≥3 tender joints with an inadequate response to ≥1 cDMARD. Patients were randomized (1:1) to Taltz or Humira and allowed to continue a stable dose of concomitant cDMARD during the study. For Taltz patients with psoriatic arthritis only (n=234), the initial dose (160 mg as 2 injections) was followed by 80 mg every 4 weeks. Humira patients (n=231) received 40 mg every other week and no initial dose. Patients who met the trial design criteria for moderate to severe psoriasis (BSA ≥10%, PASI ≥12, and sPGA ≥3) in addition to psoriatic arthritis followed the psoriasis dosing regimen: Taltz patients (n=49) received an initial dose of 160 mg (two 80 mg injections), followed by 80 mg every 2 weeks through week 12, then 80 mg every 4 weeks thereafter. Humira patients (n=52) received an initial dose of 80 mg, then 40 mg every other week starting 1 week after the initial dose.
Humira® is a registered trademark of AbbVie Biotechnology Ltd.
Reference: 1. Taltz [package insert]. Indianapolis, IN: Lilly USA, LLC.
COAST-V and -W Trial Designs (AS)1
COAST-V (N=341) and -W (N=316) were phase 3, multicenter, randomized, double-blind clinical trials designed to evaluate the efficacy and safety of Taltz compared with placebo in patients with active AS. The primary efficacy endpoint for both trials was the proportion of patients achieving ASAS40 response at week 16. Patients in COAST-V were biologic-naive. Patients in COAST-W were TNFi-experienced, meaning they had an inadequate response or were intolerant to 1 or 2 TNFis. All patients were ≥18 years of age, had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BADSAI) score ≥4, and an established diagnosis of r-axSpA with sacroiliitis defined radiographically according to the mNY criteria. Patients had at least 1 spondyloarthritis (SpA) feature per ASAS criteria and were randomized to placebo or Taltz 80 mg or 160 mg at week 0, followed by Taltz 80 mg every 2 or 4 weeks. All patients had experienced back pain for at least 3 months, with onset before the age of 45. In COAST-V, an active reference arm of Humira® (adalimumab) 40 mg every 2 weeks was included. The approved AS dose for Taltz is 160 mg at week 0 followed by 80 mg every 4 weeks.
Humira® is a registered trademark of AbbVie Biotechnology Ltd.
Reference: 1. Taltz [package insert]. Indianapolis, IN: Lilly USA, LLC.
COAST-X Trial Design (nr-axSpA)1
COAST-X was a phase 3, randomized, double-blind, clinical trial designed to evaluate the efficacy and safety of Taltz compared with placebo in patients with active nr-axSpA. The primary efficacy endpoint was the proportion of patients achieving ASAS40 response at week 52. Patients were biologic-naive and had an established diagnosis of nr-axSpA with objective signs of inflammation indicated by: sacroiliitis on MRI and/or elevated CRP (>5 mg/L) and no definitive radiographic evidence of structural damage on sacroiliac joints. All patients were ≥18 years of age and had a baseline BASDAI score ≥4. All patients had active axial spondyloarthritis for at least 3 months. Patients must have been intolerant to or had an inadequate response to at least two NSAIDs. Patients were randomized to placebo (n=105) or Taltz 80 mg or 160 mg at week 0, followed by Taltz 80 mg every 2 (n=102) or 4 (n=96) weeks. The approved dose is 80 mg every 4 weeks. At week 16 through week 44, patients were eligible to change their background therapy (NSAIDs, cDMARDs, corticosteroids, analgesics) or switch to open-label Taltz 80 mg every 2 weeks at the discretion of the investigator while remaining blind to original treatment. Patients who switched to open-label Taltz every 2 weeks were considered nonresponders.
Reference: 1. Taltz [package insert]. Indianapolis, IN: Lilly USA, LLC.
PsA=psoriatic arthritis; PsO=psoriasis; AS=ankylosing spondylitis; nr-axSpA=non-radiographic axial spondyloarthritis.
