COSENTYX clinical trial end points
FUTURE 2 studied a mixed population of patients with PsA: 2/3 biologic-naive and 1/3 anti–TNF-α inadequate responders7
FUTURE 2
ACR20 responses at Week 16 (NRI) in the mixed population were 57% (P<0.0001), 60% (P<0.0001), and 18%, respectively, for COSENTYX 300 mg (n=100), 150 mg (n=100), and placebo (n=98)1,7
The primary end point of ACR20 responses at Week 24 (NRI) was achieved by 54% of patients on COSENTYX 300 mg (n=100) (P<0.0001), 51% on COSENTYX 150 mg (n=100) (P<0.0001), and 15% on placebo (n=98)1,7
Skin lesions improved in patients with coexistent PsO who received COSENTYX (n=99) compared with placebo (n=43), as measured by the PASI1,7
Improvements in enthesitis and dactylitis scores were observed in the COSENTYX group compared with placebo at Week 241
FUTURE 5
FUTURE 5 studied a mixed population of patients with PsA: more than 2/3 biologic-naive and less than 1/3 anti–TNF-α inadequate responders18
JOINT18
ACR20 response rates (NRI) (primary end point) were:
ENTHESITIS18
Complete resolution (LEI=0) in patients with enthesitis at baseline (NRI):
DACTYLITIS18
Complete resolution (LDI=0) in patients with dactylitis at baseline (NRI):
SKIN18
Patients who achieved PASI 90 (NRI):
NAIL18*
Reduction in nail disease (mNAPSI as observed) response rates were†:
JUNIPERA
Time to flare in Treatment Period 2 in biologic-naive patients with JPsA or ERA (primary end point)17
The median time to disease flare was not reached in the COSENTYX group and was 453 days in the placebo group (KM estimate).17
MAXIMISE
MAXIMISE studied biologic-naive patients with PsA19
The primary end point (ASAS20 responses at Week 12) was achieved by 63% of patients on COSENTYX 300 mg (n=164) compared with 31% for placebo (n=164) (MI; P<0.0001)19
The key secondary end point, ASAS20 responses at Week 12 in patients on COSENTYX 150 mg, was achieved by 66% (n=157) (MI; P<0.0001)19
MEASURE 2
MEASURE 2 studied a mixed population of patients with AS: 2/3 biologic-naive and 1/3 anti–TNF-α inadequate responders12
PREVENT
PREVENT studied 90% biologic-naive patients and 10% anti–TNF-α inadequate responders with nr-axSpA20
TRANSFIGURE
TRANSFIGURE studied patients with nail psoriasis21,22
The primary end point, improvement from baseline NAPSI at Week 16 (repeated measures analysis), was 46.1% for COSENTYX 300 mg (n=63) and 11.7% for placebo (n=56) (P<0.0001)21,22
*Nail data in PsA were consistent with those in the dedicated nail PsO study, TRANSFIGURE. Improvement from baseline NAPSI at Week 16 (primary end point) (repeated measures analysis) was 46.1% for COSENTYX 300 mg (n=63) and 11.7% for placebo (n=56) (P<0.0001).22
†At baseline, mNAPSI scores were 18.0 and 17.8 in the 300-mg and 150-mg arms, respectively. At Week 16, mNAPSI scores were 8.8 and 8.4 in the 300 mg and 150 mg arms, respectively.18
Study designs
FUTURE 2 study design
FUTURE 2 was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated 397 adult patients with active PsA (≥3 swollen and ≥3 tender joints) despite use of NSAIDs, corticosteroids, or DMARDs. Patients had a diagnosis for ≥5 years and received subcutaneous COSENTYX 75 mg (n=99), 150 mg (n=100), 300 mg (n=100), or placebo (n=98) at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks thereafter. Patients who received placebo were rerandomized to COSENTYX 150 mg or 300 mg every 4 weeks at Week 16 or Week 24 based on responder status. Primary end point was the percentage of patients with ACR20 response at Week 24. Study population was mixed: 2/3 of patients were biologic-naive and 1/3 were anti–TNF-α inadequate responders.1,7,23
FUTURE 5 study design
FUTURE 5 was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that evaluated 996 adult patients with active PsA. Patients were randomized to receive subcutaneous COSENTYX 150 mg without load (n=222), 150 mg with load (n=220), 300 mg with load (n=222), or placebo (n=332). Patients who received placebo were rerandomized to receive COSENTYX 150 mg or 300 mg every 4 weeks, based on responder status at Week 16 (nonresponders) or Week 24 (responders). Primary end point was the percentage of patients with ACR20 response at Week 16. Secondary end points included change in mTSS at Week 24 from baseline. Study population was mixed: more than 2/3 of patients were biologic-naive and less than 1/3 were anti–TNF-α inadequate responders (individual patients could have been exposed to up to 3 TNF-α inhibitors).18,24
JUNIPERA study design
JUNIPERA was a 2-year, 3-treatment-period, phase 3, double-blind, placebo-controlled, event-driven, randomized-withdrawal study in 86 biologic-naive patients 2 years to <18 years of age with active JPsA or ERA as diagnosed based on modified ILAR JIA classification criteria. Treatment Period 1 consisted of all patients receiving open-label treatment with COSENTYX until Week 12. Responders (achieving JIA ACR30 response) at Week 12 entered Treatment Period 2, a double-blind, randomized period in which patients were randomized 1:1 to continue treatment with COSENTYX or begin treatment with placebo. Treatment Period 3 consisted of open-label COSENTYX. Patients were treated subcutaneously with COSENTYX 75 mg if weighing <50 kg or COSENTYX 150 mg if weighing ≥50 kg (Weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter). The primary end point was time to flare in Treatment Period 2. Disease flare was defined as ≥30% worsening in ≥3 of the 6 JIA ACR response criteria, and 30% improvement in ≤1 of the 6 JIA ACR response criteria and ≥2 active joints. Secondary end points were based on descriptive analyses.1,17
MAXIMISE study design
MAXIMISE was a randomized, double-blind, placebo-controlled, multicenter, 52-week study that evaluated 498 patients with active PsA and axial skeleton involvement (defined by BASDAI score ≥4, spinal pain VAS ≥40 [0 to 100 mm scale]) who had inadequate response to at least 2 NSAIDs for at least 4 weeks. Patients were randomized to receive subcutaneous COSENTYX 150 mg (n=165), COSENTYX 300 mg (n=167), or placebo (n=166) at Weeks 0, 1, 2, 3, 4, and 8. Primary end point was the proportion of patients with ASAS20 response at Week 12. After Week 12, patients who were placed in the placebo group at baseline were rerandomized to active treatment with COSENTYX 150 mg or 300 mg, administered every 4 weeks from Week 12 to Week 52 (last dose on Week 48), but remained blinded to dose.19
MEASURE 2 study design
MEASURE 2 was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated 219 adult patients with active AS who received COSENTYX 75 mg, 150 mg, or placebo subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks. At Week 16, patients who received placebo were rerandomized to either COSENTYX 75 mg or 150 mg every 4 weeks. After 16 weeks, patients knew they were taking active medication, but were blinded to the dose. After 1 year, patients continued to receive the same active dose as open-label treatment and were assessed every 8 weeks through 2 years, then every 12 weeks through 5 years. The primary end point was the percentage of patients who achieved ASAS20 response at Week 16.1,12,13
PREVENT study design
PREVENT was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that evaluated 555 adult patients with active nr-axSpA who met the ASAS classification criteria for axSpA and had abnormal hsCRP and/or evidence of sacroiliitis on MRI. Participants were randomized to receive 1 of 3 treatments subcutaneously: COSENTYX 150 mg load, COSENTYX 150 mg no load, or placebo. Patients were treated with COSENTYX 150 mg with load or placebo (Weeks 0, 1, 2, 3, and 4) or COSENTYX 150 mg without load (Weeks 0 and 4), followed by the same dose every 4 weeks thereafter. Starting at Week 16, dose adjustment or addition of concomitant NSAIDs and DMARDs was permitted. Starting at Week 20, patients were allowed to switch to open-label COSENTYX 150 mg monthly or local standard of care if the patient was considered an inadequate responder for 2 consecutive visits by the discretion of the investigator and patient. The primary end point was the percentage of biologic-naive patients who achieved ASAS40 response at Week 52 in the no-load arm. The core phase of the trial ran through Week 104, with an extension phase through Week 208. Most patients (90%) were biologic-naive in this study.1,15,20
TRANSFIGURE study design
TRANSFIGURE was a double-blind, randomized, placebo-controlled study examining the safety and efficacy of COSENTYX in patients with moderate to severe nail PsO. Patients were randomized to COSENTYX 300 mg (n=66), COSENTYX 150 mg (n=67), or placebo (n=65). All patients were adults with moderate to severe PsO (PASI score ≥12 and BSA ≥10%) and significant nail involvement (fingernail NAPSI score of ≥16 and ≥4 fingernails involved), who were candidates for systemic therapy. Primary end point: NAPSI assessment at Week 16. Secondary end points included NAPSI response over time up to Week 132.21
ACR, American College of Rheumatology; AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis international Society criteria; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BSA, body surface area; CI, confidence interval; DMARDs, disease-modifying antirheumatic drugs; ERA, enthesitis-related arthritis; HR, hazard ratio; hsCRP, high-sensitivity C-reactive protein; ILAR, International League of Associations for Rheumatology; JIA, juvenile idiopathic arthritis; JPsA, juvenile psoriatic arthritis; KM, Kaplan-Meier; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MI, multiple imputation; mNAPSI, modified Nail Psoriasis Severity Index; MRI, magnetic resonance imaging; mTSS, modified Total Sharp Score; NAPSI, Nail Psoriasis Severity Index; nr-axSpA, non-radiographic axial spondyloarthritis; NRI, nonresponder imputation; NSAIDs, nonsteroidal anti-inflammatory drugs; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsO, plaque psoriasis; TNF, tumor necrosis factor; VAS, visual analog scale.
