Search

Objective To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study. Methods Patients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c. secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load regimens or placebo at baseline, at weeks 1, 2 and 3 and every 4 weeks starting at week 4. Radiographic progression was assessed by change in van der Heijde-modified total Sharp score (vdH-mTSS; mean of two readers). Statistical analysis used a linear mixed-effects model (random slope) at weeks 24 and 52, and observed data at week 52. Assessments at week 52 included additional efficacy endpoints (non-responders imputation and mixed-effects models for repeated measures) and safety. Results The majority (86.6%) of patients completed 52 weeks of treatment. The proportion of patients with no radiographic progression (change from baseline in vdH-mTSS ⩽0.5) was 91.8, 85.2 and 87.2% in 300, 150 and 150 mg no load groups, respectively, at week 52. The change in vdH-mTSS from baseline to week 52 using random slope [mean change (s. e.)] was –0.18 (0.17), 0.11 (0.18) and –0.20 (0.18) in 300, 150 and 150 mg no load groups, respectively; the corresponding observed data [mean change (s. d.)] was –0.09 (1.02), 0.13 (1.39) and 0.21 (1.15). Clinical efficacy endpoints were sustained, and no new or unexpected safety signals were reported through 52 weeks. Conclusion Secukinumab 300 and 150 mg with or without s.c. loading regimen provided sustained low rates of radiographic progression through 52 weeks of treatment. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , NCT02404350. [ABSTRACT FROM AUTHOR]

Background and Objective: Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, has demonstrated low radiographic progression over 4 years in patients with ankylosing spondylitis (AS). An adalimumab (tumor necrosis factor [TNF] inhibitor) biosimilar, GP2017 (SDZ-ADL; Sandoz), has been approved by the European Medicines Agency (July 2018) for use in all same indications as adalimumab, including AS. Adalimumab has also shown low long-term radiographic progression in patients with AS. Direct comparison of radiographic progression in AS between IL-17A and TNF inhibitors has not been studied. SURPASS is the first head-to-head, Phase IIIb, randomized, biologic-controlled study in AS to compare effects of secukinumab versus SDZ-ADL on spinal radiographic progression. Methods: Overall, 858 biologic-naïve patients with AS with elevated high-sensitivity C-reactive protein (≥ 5 mg/L) and/or at least one syndesmophyte in the cervical/lumbar spine at baseline (without total ankylosis) were randomized (1:1:1) to subcutaneous (sc) secukinumab (300 or 150 mg) or SDZ-ADL (40 mg). Secukinumab will be administered at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 100. SDZ-ADL will be administered every 2 weeks from baseline until week 102. Patients and investigators will be unblinded to drug but blinded to secukinumab doses. Spinal X-rays will be obtained at baseline, and weeks 52 and 104, sacroiliac joint (SIJ) X-rays at baseline and week 104, and magnetic resonance imaging (MRI) of SIJs and spine at baseline, weeks 16, 52, and 104. The primary endpoint is to demonstrate superiority of secukinumab (300 or 150 mg) treatment versus SDZ-ADL regarding proportion of patients with no radiographic progression (change from baseline in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤ 0.5) at week 104. Secondary endpoints include change from baseline in mSASSS, proportion of patients with syndesmophyte at baseline who develop no new syndesmophytes, reduction of osteitis on MRI of SIJs and spine (Berlin method). Assessment of SpondyloArthritis International Society (ASAS) 20/40 responses, ASAS partial remission, and AS Disease Activity Score (ASDAS) inactive disease (ASDAS < 1.3) in secukinumab- versus SDZ-ADL-treated patients at week 104. Conclusion: This is the first study designed to evaluate superiority of an IL-17A inhibitor, secukinumab, over a TNF inhibitor, SDZ-ADL, in reducing spinal radiographic progression in AS. Study Registration: ClinicalTrials.gov, NCT03259074. [ABSTRACT FROM AUTHOR]

In ankylosing spondylitis (AS), structural damage that occurs as a result of syndesmophyte formation and ankylosis of the vertebral column is irreversible. Structural damage is currently assessed by conventional radiography and scoring systems that reliably assess radiographic structural damage are needed to capture the differential effects of drugs on structural damage progression. The validity of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) as a primary outcome measure in evaluating the effect of AS treatments on radiographic progression rates was assessed in this review. The mSASSS has not been used, to date, as a primary outcome measure in a prospective randomized controlled clinical trial of biologic therapy in AS. This review of the medical literature confirmed that the mSASSS is the most validated and widely used method for assessing radiographic progression in AS, correlating with worsening measures of disease signs and symptoms, spinal mobility and physical function, with a 2-year interval being required to ensure sufficient sensitivity to change. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic changes through 2 years in patients with ankylosing spondylitis (AS).Methods: In the phase III MEASURE 1 study, patients were randomised to receive intravenous secukinumab 10 mg/kg (at baseline, week 2 and week 4) followed by subcutaneous secukinumab 150 mg (intravenous 150 mg; n=125) or 75 mg (intravenous 75 mg; n=124) every four weeks, or matched placebo (n=122). Placebo-treated patients were re-randomised to subcutaneous secukinumab 150 or 75 mg from week 16. Clinical efficacy assessments included Assessment of SpondyloArthritis international Society 20 (ASAS20) response rates through week 104. Radiographic changes at week 104 were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).Results: 97 (77.6%) and 103 (83.1%) patients in the intravenous 150 mg and intravenous 75 mg groups, respectively, completed week 104. In the full analysis set (intent-to-treat), ASAS20 response rates at week 104 were 73.7% and 68.0% in the intravenous 150 mg and intravenous 75 mg groups, respectively. Among patients with evaluable X-rays who were originally randomised to secukinumab (n=168), mean change in mSASSS from baseline to week 104 was 0.30±2.53. Serious adverse events were reported in 12.2% and 13.4% of patients in the 150 mg and 75 mg groups, respectively.Conclusions: Secukinumab improved AS signs and symptoms through 2 years of therapy, with no unexpected safety findings. Data from this study suggest a low mean progression of spinal radiographic changes, which will need to be confirmed in longer-term controlled studies.Trial Registration Number: NCT01358175. [ABSTRACT FROM AUTHOR]