Grade 2 on spinal X-ray according to the modified New York Radiological Grade, indicative of axial spondyloarthropathy. Study 2 This multi-center, open-label, phase 4, 3-period study evaluated the withdrawal and retreatment of etanercept in patients with active nr-AxSpa who achieved an adequate response (inactive disease defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive protein (CRP) less than 1.3) following 24 weeks of treatment.
209 adult patients with active nr-AxSpa (18 to 49 years of age), defined as those patients meeting the Assessment of SpondyloArthritis International Society (ASAS) classification criteria of axial spondyloarthritis (but not meeting the modified New York criteria for AS), having positive MRI findings (active inflammation on MRI highly suggestive of sacroiliitis associated with SpA) and/or positive hsCRP (defined as high sensitivity C-reactive protein [hsCRP] >3 mg/l), and active symptoms defined by an ASDAS CRP greater than or equal to 2.1 at the screening visit received open-label etanercept 50 mg weekly plus stable background NSAID at the optimal tolerated anti inflammatory dosage for 24 weeks in Period 1.
Patients were also required to have an inadequate response or intolerance to two or more NSAIDs. At week 24, 119 (57%) patients achieved inactive disease and entered into the Period 2 40-week withdrawal phase where subjects discontinued etanercept, yet maintained the background NSAID. The primary measure of efficacy was the occurrence of flare (defined as an ASDAS erythrocyte sedimentation rate (ESR) greater than or equal to 2.1) within 40 weeks following withdrawal of etanercept. Patients who flared were retreated with etanercept 50 mg weekly for 12 weeks (Period 3).
In Period 2, the proportion of patients experiencing ≥1 flare increased from 22% (25/112) at week 4 to 67% (77/115) at week 40. Overall, 75% (86/115) patients experienced a flare at any time point within 40 weeks following withdrawal of etanercept. The key secondary objective of Study 2 was to estimate time to flare after withdrawal of etanercept and additionally compare the time to flare to patients from Study 1 who met the Study 2 withdrawal phase entry requirements and continued etanercept therapy. The median time to flare following withdrawal of etanercept was 16 weeks (95% CI: 13-24 weeks).
Less than 25% of patients in Study 1 who did not have treatment withdrawn experienced a flare over the equivalent 40-weeks as in Period 2 Study 2. The time to flare was statistically significantly shorter in subjects who discontinued etanercept treatment (Study 2) compared to subjects who received continuous etanercept treatment (Study 1), p Of the 87 patients who entered Period 3 and were retreated with etanercept 50 mg weekly for 12 weeks, 62% (54/87) reachieved inactive disease, with 50% of them reachieving it within 5 weeks (95% CI: 4 8 weeks). Adult patients with plaque psoriasis Etanercept is recommended for use in patients as defined in section 4.1.
Patients who “failed to respond to” in the target population is defined by insufficient response (PASI worsening of the disease while on treatment, and who were adequately dosed for a sufficiently long duration to assess response with at least one of the three major systemic therapies as available. The efficacy of etanercept versus other systemic therapies in patients with moderate to severe psoriasis (responsive to other systemic therapies) has not been evaluated in studies directly comparing etanercept with other systemic therapies. Instead, the safety and efficacy of etanercept were assessed in four randomised, double-blind, placebo-controlled studies.
The primary efficacy endpoint in all four studies was the proportion of patients in each treatment group who achieved the PASI 75 (i.e., at least a 75% improvement in the Psoriasis Area and Severity Index score from baseline) at 12 weeks. 24