Brian Porter

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

BACKGROUND Secukinumab is an anti-interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. METHODS In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. RESULTS In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohns disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. CONCLUSIONS Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.).

Secukinumab efficacy in anti-TNF-naive and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the MEASURE 2 Study

Background There is significant unmet need in patients with ankylosing spondylitis (AS) who have inadequate response or intolerance to anti-tumour necrosis factor (TNF) treatment. Secukinumab, an anti-interleukin-17A monoclonal antibody, significantly improved signs and symptoms of AS in the MEASURE 2 study (NCT01649375). Methods Subjects with active AS (N=219) received secukinumab (150 or 75 mg) or placebo at baseline, weeks 1, 2, 3 and 4, and every 4 weeks thereafter. Randomisation was stratified by prior anti-TNF use: anti-TNF-naive or inadequate response/intolerance to one anti-TNF (anti-TNF-IR). The primary endpoint was Assessment of SpondyloArthritis International Society criteria (ASAS) 20 at week 16. Results At week 16, 68.2% of anti-TNF-naive subjects treated with secukinumab 150 mg achieved ASAS20 compared with 31.1% treated with placebo (p<0.001). In the anti-TNF-IR group, 50.0% of subjects treated with secukinumab 150 mg achieved an ASAS20 response compared with 24.1% treated with placebo (p<0.05). Numerically greater improvements were observed with secukinumab than with placebo for most secondary endpoints. Clinical responses were sustained through week 52. Conclusions Secukinumab 150 mg provided sustained improvements in signs and symptoms of AS in anti-TNF-naive and anti-TNF-IR subjects through 52 weeks of therapy. Trial registration number NCT01649375.

Efficacy and Safety of Subcutaneous and Intravenous Loading Dose Regimens of Secukinumab in Patients with Active Rheumatoid Arthritis: Results from a Randomized Phase II Study.

Objective. To evaluate the efficacy and safety of secukinumab, a fully human antiinterleukin-17A monoclonal antibody, administered with an intravenous (IV) or subcutaneous (SC) loading regimen versus placebo, in patients with active rheumatoid arthritis (RA). Methods. In this phase II, double-blind, double-dummy, 52-week study (ClinicalTrials.gov NCT01359943), 221 patients with inadequate response to methotrexate were randomized (2:2:1) to secukinumab, IV loading 10 mg/kg at baseline, Weeks 2 and 4, then SC 150 mg every 4 weeks (n = 88); secukinumab SC loading 150 mg once weekly for 5 weeks, then every 4 weeks (n = 89); or a matching placebo (followed by secukinumab 150 mg every 4 weeks starting Week 16; n = 44). The primary endpoint was superior efficacy of pooled secukinumab versus placebo using American College of Rheumatology 20% response (ACR20) at Week 12. Results. The primary efficacy endpoint was not met: ACR20 response at Week 12 was 49.2% for pooled secukinumab versus 40.9% for placebo (p = 0.3559). These variables improved significantly with pooled secukinumab versus placebo at Week 12 (all p < 0.05): the 28-joint Disease Activity Score (DAS28), patient’s and physician’s global assessment of disease activity, patient’s assessment of RA pain, and high-sensitivity C-reactive protein levels. Results of continuous efficacy outcomes were similar between the IV and SC loading regimens. The most frequent adverse events were infections, with similar rates across secukinumab and placebo. Conclusion. Although the primary endpoint (ACR20) was not met, secukinumab demonstrated improved efficacy in reducing disease activity over placebo as measured by DAS28 and other secondary endpoints.

Secukinumab and Sustained Improvement in Signs and Symptoms of Patients With Active Ankylosing Spondylitis Through Two Years: Results From a Phase III Study

Secukinumab improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks in the phase III MEASURE 2 study. Here, we report longer‐term (104 weeks) efficacy and safety results.

Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3

BackgroundSecukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen.MethodsA total of 226 patients were randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables.ResultsThe primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P < 0.01) and IV-150 mg (58.1%; P < 0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3–4 neutropenia were 1.8% for both of these adverse events in secukinumab-treated patients.ConclusionsSecukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings.Trial registrationClinicalTrials.gov, NCT02008916. Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.

Effect of Secukinumab on Patient-Reported Outcomes in Patients With Active Ankylosing Spondylitis A Phase III Randomized Trial (MEASURE 1)

To evaluate the effect of secukinumab (interleukin‐17A inhibitor) on patient‐reported outcomes in patients with active ankylosing spondylitis (AS).

THU0210 Secukinumab Efficacy in Anti-Tnf-Naive Patients and Patients Previously Exposed to Anti-Tnf Therapy: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study (Measure 2) in Active Ankylosing Spondylitis

Background Current treatment options for ankylosing spondylitis (AS) patients with intolerance or an inadequate response to tumor necrosis factor alpha inhibitors (anti-TNF) are limited. Secukinumab, a human anti–interleukin-17A monoclonal antibody, significantly improved the signs and symptoms of AS in the phase 3 MEASURE 2 study (NCT01649375).1 Objectives To evaluate the efficacy and safety of secukinumab by anti-TNF history in the MEASURE 2 study. Methods 219 adults with active AS were randomized to receive subcutaneous (s.c.) secukinumab (150 or 75 mg) or PBO at baseline, Wk 1, 2 and 3, and every 4 wks starting at Wk 4. Randomization was stratified according to prior anti-TNF experience: anti-TNF-naive, or inadequate response or intolerance to not more than one anti-TNF biologic agent (anti-TNF-IR). At Wk 16, PBO-treated subjects were re-randomized to secukinumab 150 or 75 mg. Pre-planned subgroup analyses of the primary and secondary endpoints were conducted among anti-TNF-naive and anti-TNF-IR subjects and included: the proportion of subjects achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 response (primary endpoint), ASAS40, high sensitivity C-reactive protein (hsCRP), ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Short Form-36 (SF-36), Ankylosing Spondylitis Quality of Life (ASQoL), and ASAS partial remission. Analyses at Wk 16 used non-responder imputation (for binary variables) and mixed-effects repeated measures model (for continuous variables). Wk 52 data are as observed. Results 62% of subjects enrolled were anti-TNF-naive and 38% were anti-TNF-IR. At Wk 16, secukinumab 150 mg (but not 75 mg) improved ASAS20 response rates compared with PBO in both anti-TNF-naive (68.2% vs 31.1%, respectively; P<0.001) and anti-TNF-IR (50.0% vs 24.1%; P<0.05) subjects. Improvements with secukinumab 150 mg were observed for all secondary endpoints in anti-TNF-naive subjects, except ASAS partial remission, and for most secondary endpoints in anti-TNF-IR subjects (Table). Clinical responses to secukinumab were sustained or continued to improve in both anti-TNF-naive and anti-TNF-IR subjects through 52 wks of therapy (Table). Conclusions Secukinumab 150 mg s.c. provided sustained improvement in the signs and symptoms of AS, with associated reduction in inflammation and improvement in physical function and health-related QoL in both anti-TNF-naive and anti-TNF-IR subjects. References Sieper J, et al. Arthritis Rheumatol. 2014;66(11 Suppl):S232. Acknowledgements Medical writing support was provided by Jessica Breen at Seren Communications (Tytherington, UK), and was funded by Novartis. Disclosure of Interest J. Sieper Grant/research support from: AbbVie, Pfizer, and Merck, Consultant for: AbbVie, Pfizer, Merck, UCB, and Novartis, Speakers bureau: AbbVie, Pfizer, Merck, and UCB, J. Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, Consultant for: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, X. Baraliakos Grant/research support from: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, Consultant for: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, Speakers bureau: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, D. Baeten Grant/research support from: Boehringer-Ingelheim, Janssen, MSD, Novartis, and Pfizer, Consultant for: AbbVie, Boehringer-Ingelheim, BMS, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, M. Dougados Grant/research support from: AbbVie, BMS, Eli Lilly, Merck, and Pfizer, Consultant for: Eli Lilly, P. Emery Consultant for: AbbVie, BMS, Merck, Novartis, Pfizer, Roche, and UCB, A. Deodhar Grant/research support from: AbbVie, Celgene, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Celgene, Janssen, Novartis, Pfizer, and UCB, B. Porter Shareholder of: Novartis, Employee of: Novartis, M. Andersson Employee of: Novartis, H. Richards Employee of: Novartis

SAT0396 Secukinumab Provides Sustained Improvements in The Signs and Symptoms of Active Ankylosing Spondylitis: 2-Year Results from A Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing (Measure 2)

Background Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks (wks) in the randomised, double-blind, placebo (PBO)-controlled, Phase 3 MEASURE 2 study (NCT01649375).1 Objectives To evaluate the long-term (104 wks) efficacy and safety of secukinumab in MEASURE 2 study. Methods 219 subjects with active AS, classified by modified New York criteria, despite therapy with NSAIDs, were randomised to subcutaneous (s.c.) secukinumab 150 or 75 mg or PBO at baseline (BL), Wks 1, 2 and 3, and every 4 wks (q4w) from Wk 4. At Wk 16, PBO-treated subjects were re-randomised to secukinumab 150 or 75 mg s.c. q4w. At BL, 39% of subjects had an inadequate response/intolerance to prior anti-TNF therapy (anti–TNF-IR). Primary endpoint was ASAS20 response rates at Wk 16. Secondary endpoints included ASAS40, hsCRP, ASAS5/6, BASDAI, SF-36 PCS and ASAS partial remission. Endpoints were assessed through Wk 104, with multiple imputation for binary variables and a mixed-model repeated measures for continuous variables. Analyses stratified by anti-TNF history were pre-specified and are reported as observed. Results 60/72 (83.3%), 57/73 (78.1%) and 57/74 (77%) subjects completed 104 wks of treatment with secukinumab 150 mg, 75 mg and PBO, respectively. As reported previously, secukinumab 150 mg significantly improved all pre-specified endpoints at Wk 16 vs. PBO, except ASAS partial remission; the 75 mg dose did not reach statistical significance at Wk 16 based on hierarchical testing.1 ASAS20/40 response rates at Wk 104 were 71.5/47.5% with both secukinumab doses. Clinical improvements with secukinumab were sustained through Wk 104 across all secondary endpoints (Table). In the subgroup of anti–TNF-naïve subjects, ASAS20/40 response rates at Wk 104 (observed data) were 76.9/56.4% and 80.0/60.0% with secukinumab 150 mg and 75 mg, respectively; corresponding rates in anti–TNF-IR subjects were 85.0/50.0% and 68.8/43.8%. Across the treatment period (mean secukinumab exposure: 735.6 days), exposure-adjusted incidence rates for serious infections/infestations, IBD, malignant/unspecified tumours and MACE with secukinumab were 1.2, 1.4, 0.5 and 0.7 per 100 subject-years, respectively. No cases of TB, opportunistic infections or suicidality-related AEs were reported. Conclusions Secukinumab provided sustained improvement through 2 years in the signs and symptoms of AS with improved physical function, regardless of anti-TNF status. Safety was consistent with previous reports. References Baeten D et al. N Engl J Med 2015;373:2534–48 Disclosure of Interest H. Marzo-Ortega Grant/research support from: Janssen and Pfizer, Consultant for: Abbvie, Celgene, Janssen, Novartis and UCB, Speakers bureau: Abbvie, Celgene, Janssen and UCB, C. Legerton Grant/research support from: AbbVie, Ablynx, Acerta, Amgen, AstraZeneca, Celgene, GSK, Janssen, E. Lilly, BMS, Pfizer, Novartis, Sandoz, UCB, Daiichi Sankyo, ChemoCentryx, Boehringer Ingelheim, Speakers bureau: Celgene and Amgen, J. Sieper Grant/research support from: AbbVie, Pfizer and Merck, Consultant for: AbbVie, Pfizer, Merck, UCB and Novartis, Speakers bureau: AbbVie, Pfizer, Merck and UCB, A. Kivitz Consultant for: AbbVie, Pfizer, Genentech, UCB and Celgene, Speakers bureau: Celgene, Pfizer, and Genentech, R. Blanco: None declared, M. Cohen Consultant for: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB, J. Zuazo Employee of: Novartis, A. Readie Shareholder of: Novartis, Employee of: Novartis, B. Porter Shareholder of: Novartis, Employee of: Novartis, H. Richards Employee of: Novartis

OP0168 Secukinumab Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: 52-Week Data from Measure 2, A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing

Background In MEASURE 2 (NCT01649375), subcutaneous (s.c.) administration of secukinumab improved the signs and symptoms of ankylosing spondylitis (AS) through 16 weeks (wks) of therapy.1 Objectives To investigate the long-term (52 wks) efficacy and safety of s.c. secukinumab in the MEASURE 2 study. Methods 219 adults with active AS, despite therapy with nonsteroidal anti-inflammatory drugs, were randomized to receive s.c. secukinumab 150 mg, 75 mg, or placebo (PBO) at baseline, Wk 1, 2, and 3, and every 4 wks starting from Wk 4. At Wk 16, subjects in the PBO group were re-randomized to secukinumab 150 mg or 75 mg every 4 wks. The primary endpoint was the proportion of subjects achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 response at Wk 16. Secondary endpoints included ASAS40, high sensitivity C-reactive protein (hsCRP), ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity (BASDAI), Short Form-36 Health Survey Physical Component Summary (SF-36 PCS), Ankylosing Spondylitis Quality of Life (ASQoL), and ASAS partial remission. Statistical analyses at Wk 16 used non-responder imputation (binary variables) and mixed-effects repeated measures model (continuous variables) following a pre-defined hierarchical hypothesis testing strategy to adjust for multiplicity of testing. Wk 52 data are as observed. Results 181 pts (82.6%) completed 52 wks of treatment. ASAS20 response rate at Wk 16 was 61.1% with secukinumab 150 mg vs 28.4% with PBO (P=0.0001). Secukinumab 150 mg also significantly improved hsCRP, ASAS40, ASAS 5/6, BASDAI, SF-36 PCS and ASQoL at Wk 16, compared with PBO. Clinical responses with secukinumab 75 mg did not reach statistical significance for any of the pre-specified endpoints based on hierarchical testing. Improvements with secukinumab 150 mg were sustained through Wk 52; ASAS20/40 response rates with secukinumab 150 mg were 73.8%/57.4% at Wk 52 (observed data). ASAS20/40 response rates in subjects originally randomized to PBO who received secukinumab 150 mg (n=34) were 75.0%/56.3% at Wk 52. Exposure-adjusted adverse event (AE) rates (mean secukinumab exposure: 425.8 days; mean PBO exposure: 107.6 days) were 214.1, 211.7 and 443.2 per 100 patient-years with secukinumab 150 mg, 75 mg and PBO, respectively. The respective rates of serious AEs were 6.6, 7.7 and 14.0. The most common serious AE (SAE) was serious infections; no subject discontinued therapy due to a SAE. Conclusions Secukinumab 150 mg s.c. provided sustained improvements to 52 weeks in the signs and symptoms of AS, reducing inflammation, and improving physical function and health-related quality of life. Secukinumab was well tolerated; safety findings were consistent with previous reports. References Sieper J, et al. Arthritis Rheumatol. 2014;66(11Suppl):S232 Acknowledgements Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis. Disclosure of Interest J. Sieper Grant/research support from: AbbVie, Pfizer, and Merck, Consultant for: AbbVie, Pfizer, Merck, UCB, and Novartis, Speakers bureau: AbbVie, Pfizer, Merck, and UCB, J. Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, Consultant for: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB, X. Baraliakos Grant/research support from: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, Consultant for: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, Speakers bureau: AbbVie, Merck, Pfizer, UCB, Novartis, and Chugai, D. Baeten Grant/research support from: Boehringer-Ingelheim, Janssen, MSD, Novartis, and Pfizer, Consultant for: AbbVie, Boehringer-Ingelheim, BMS, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, M. Dougados Grant/research support from: AbbVie, BMS, Eli Lilly, Merck, and Pfizer, Consultant for: Eli Lilly, P. Emery Consultant for: AbbVie, BMS, Merck, Novartis, Pfizer, Roche, and UCB, A. Deodhar Grant/research support from: AbbVie, Celgene, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Celgene, Janssen, Novartis, Pfizer, and UCB, J. Wei Grant/research support from: BMS, Janssen, Pfizer, Sanofi-Aventis, and Novartis, Consultant for: Pfizer, Celgene, Chugai, UCB Pharma, and TSH Taiwan, Speakers bureau: Abbott, BMS, Chugai, Eisai, Janssen, and Pfizer, B. Porter Shareholder of: Novartis, Employee of: Novartis, M. Andersson Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, H. Richards Employee of: Novartis

Modified stoke ankylosing spondylitis spinal score as an outcome measure to assess the impact of treatment on structural progression in ankylosing spondylitis

Abstract 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.