Secukinumab In Patients Research Articles

Secukinumab in patients with psoriasis who have responded inadequately to tumour necrosis factor inhibitor treatment.

Linked Article:Warren et al. Br J Dermatol 2020; 183:60–70.

Outcomes With Treatment and Withdraw of Secukinumab in Patients With Plaque Psoriasis

Outcomes With Treatment and Withdraw of Secukinumab in Patients With Plaque Psoriasis

Effectiveness and safety of secukinumab in patients with moderate-to-severe plaque psoriasis - a real life retrospective study.

IntroductionClinical experience indicates that secukinumab has significant efficacy in the treatment of moderate-to-severe psoriasis and psoriatic arthritis, demonstrating a rapid onset of action, sustained response, a favourable safety profile, and an improvement of patients’ quality of life.AimTo analyse the effects of skin lesions, signs and symptoms of arthritis, quality of life and safety of treatment in patients with psoriasis and psoriatic arthritis treated with secukinumab.Material and methodsThe study included 38 subjects, 21 with psoriasis (PV) and 17 with psoriatic arthritis (PsA) who received ≥ 1 dose of secukinumab. We assessed response to secukinumab treatment by the Psoriasis Area and Severity Index (PASI), body surface area (BSA), the Dermatology Life Quality Index (DLQI), moreover in patients with PsA, we also assessed 5-point Likert scale and joint tenderness and swelling. We evaluated the safety profile of secukinumab by assessing laboratory tests and monitoring adverse reactions.ResultsIn patients with PV a statistically significant decrease in PASI (from 21.46 points to 0.84 point), BSA (from 22.38% to 0.8%), DLQI (from 20.57 points to 0.33 point) was observed. In patients with PsA a statistically significant decrease in PASI (from 13.41 points to 0.0 point), BSA (from 14.59% to 1.0%) and DLQI (from 17.76 points to 0.67 point) was observed. We noticed three incidences of adverse events.ConclusionsOur results prove that secukinumab offers a good therapeutic opportunity and may be a preferred treatment option for patients with moderate-to-severe psoriasis and psoriatic arthritis.

Spondyloarthritis: management algorithms and experience of target therapy

The article presents current data on algorithms for managing patients with the most common forms of spondylarthritis — ankylosing spondylitis, axial spondylarthritis and psoriatic arthritis, based on existing national and European recommendations. The analysis of innovative approaches to the patho‑genetic therapy of spondyloarthritis with special attention to the inhibition of interleukin‑17 using the drug secukinumab. Along with the literature data, there is a clinical experience of using secukinumab in patients with ankylosing spondylitis, axial spondyloarthritis, and psoriatic arthritis. It has been shown that secukinumab can improve the quality of treatment and achieve clinical remission in patients with high disease activity and adverse prognostic factors. In connection with the high efficacy and safety of treatment, the feasibility of using secukinumab as a first‑line biological agent with insufficient response to a standard basic drug is discussed.

LB1106 An exploratory open label phase 1b study of secukinumab in patients with moderate to severe papulopustular rosacea

LB1106 An exploratory open label phase 1b study of secukinumab in patients with moderate to severe papulopustular rosacea

Effectiveness and security of secukinumab in patients with moderate to severe psoriasis in real clinical practice in a tertiary referral hospital

Effectiveness and security of secukinumab in patients with moderate to severe psoriasis in real clinical practice in a tertiary referral hospital

P055 Development of Crohn's disease with use of secukinumab

BACKGROUND: Secukinumab is an anti-IL-17a monoclonal antibody approved for the treatment of ankylosing spondylitis, plaque psoriasis, and psoriatic arthritis. IL-17 has been associated with both pro- and anti-inflammatory properties. Mice studies suggest a beneficial role of IL 17a in the gut, as its inhibition reduces the recruitment of neutrophils, resulting in gut inflammation. Hueber et al. (2012) conducted a RCT of secukinumab in patients with moderate to severe CD, which was terminated prematurely due to worsening of Crohns symptoms, other adverse events, and lack of efficacy. We present an interesting case of IL-17 blockade induced inflammatory bowel disease. CASE: A 36-year-old male with history of refractory psoriasis most recently treated with secukinumab presented to the ED with complaint of abdominal bloating, fever, lower extremity lesions and diarrhea ×14 days. He was previously treated with methotrexate, etanercept, ustekinumab and adalimumab. Secukinumab was started 2 years before presentation, but was held in the setting of abnormal LFTs. A chronic liver disease workup was negative including a non-diagnostic liver biopsy. He restarted secukinumab approximately 7 months prior to his presentation. Patient presented with diarrhea for the preceding 2 weeks, consisting of at least 5 loose, non-bloody BMs per day. He also noted several lesions on his lower extremity for which his dermatologist obtained biopsy, consistent with erythema nodosum. He noted no prior history of any gastrointestinal symptoms and no family history of IBD. At the time of evaluation examination was notable for mild abdominal distention and right sided tenderness without guarding. Workup included mild leukocytosis at 11,700 with left shift, CRP 255, stool studies negative for c. diff, fecal lactoferrin was positive. A diagnostic colonoscopy was performed and there was evidence of severe colitis with stellate ulcers and friability involving the right colon extending through the transverse colon. The terminal ileum, left colon and rectum were spared. Biopsy demonstrated chronic colitis with markedly active ulceration and the patient was discharged on a prednisone taper. A colonoscopy was repeated 1 month after his prednisone was tapered, and there was evidence of scarring and pseudopolyps, but no inflammation. Biopsies demonstrated inactive chronic colitis. Given clinical and endoscopic remission, he was monitored off biologic therapy specifically for IBD. He was started on guselkumab, an anti-IL-23 agent, for his psoriasis. Ten months later, he remains in clinical remission with an undetectable fecal calprotectin. DISCUSSION: Our case provides a challenging dilemma regarding secukinumab and whether use led to unmasking of a subclinical IBD, induction of denovo IBD, or development of a drug-induced colitis. We suspect that the inhibition of IL-17a initiated an inflammatory cascade that led to the development of Crohn's disease, and the presence of extra intestinal manifestation (biopsy proven erythema nodosum) supports this. Our case serves to raise awareness that use of secukinumab can lead to IBD. All providers should have a high index of suspicion for the development or unmasking of IBD with use of secukinumab, and use caution in those with genetic susceptibility.

Effectiveness and safety of secukinumab in Italian patients with psoriasis: an 84 week, multicenter, retrospective real-world study

ABSTRACTBackground: Long term data on the real-life use of secukinumab are scant. The aim of this study was to investigate the real-life effectiveness, safety and treatment persistence of secukinumab in patients with moderate-to-severe psoriasis.Research design and methods: This 84-week, multicenter (n = 7) retrospective study analyzed data from patients who initiated and received at least 6 months of secukinumab treatment between June 2016 and June 2018 in the Campania region of Italy. Patient demographic and treatment characteristics, duration of treatment and reasons for discontinuation as well as Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores were assessed.Results: 324 patients (63% male, mean age 50.2 years) were enrolled and received a mean 11.7 months of secukinumab treatment. Overall, 9.5% discontinued secukinumab, including 5.2% who discontinued due to secondary inefficacy and 1.8% due to adverse events. PASI, BSA and DLQI scores were significantly improved from baseline at every follow-up visit (p < 0.001) and mean PASI decreased from 15.3 ± 6.3 at baseline to 0.5 ± 1.0 at week 84. Secukinumab had comparable effectiveness in biologic naïve and non-naïve patients.Conclusions: This study confirmed the effectiveness and safety of secukinumab in real-world patients with psoriasis.

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data

BackgroundSecukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS).MethodsThe integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab.ResultsA total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs.ConclusionsSecukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.

Clinical utility of secukinumab in moderate-to-severe scalp psoriasis: evidence to date.

Psoriasis is an immune-mediated inflammatory dermatosis commonly affecting the scalp and fringes of the face, neck and ears. It may be difficult to treat and the presence of extensive and highly visible lesions may significantly influence psychosocial well-being. Secukinumab, a monoclonal antibody that selectively targets interleukin-17A and has been shown to provide robust and sustained efficacy for whole body psoriasis. In this review, we evaluate the evidence to date of secukinumab in patients with moderate-to-severe scalp psoriasis. A comprehensive Cochrane database and PubMed searches of all available literature in English through September 2018 was performed using the search terms: “psoriasis”, “scalp” and “secukinumab”. Based on current evidence, we conclude that secukinumab is efficacious and well-tolerated treatment for patients with moderate-to-severe scalp psoriasis. Further studies are however warranted.

Comparing the efficacy and safety of IL-17 inhibitors for treatment of moderate-to-severe psoriasis: a randomized double blind pilot study with a review of literature.

Psoriasis is a chronic skin disease in which interleukin-17A (IL-17A) has been found to play an important role. Commercially available anti-IL-17 drugs include brodalumab, ixekizumab (IXE), and secukinumab (SEC). To compare the safety and efficacy of IXE and SEC in patients with moderate-to-severe plaque psoriasis. The patients were randomized to the IXE or SEC group. Effectiveness was estimated by Physician's Global Assessment (PGA), Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI). Safety was assessed by documentation of adverse effects (AEs), routine laboratory values, and injection-site and allergic reactions. There were 155 patients in the IXE group and 158 in the SEC group. At week 12, PASI 75 was 76.77% (IXE) vs. 67.09% (SEC); PASI 90 42.58% (IXE) vs. 32.28% (SEC); PGA score of 0 or 1 at week 40 (79.52% vs. 74.4%) and at week 52 (61.83% vs. 58.12%) (p < 0.001). Also, DLQI score improvement was more pronounced in the IXE group. The rates and types of AEs were similar in both groups. Although both groups demonstrated a robust clinical response, a significant improvement in patient quality of life, and a satisfactory safety profile, the IXE group scored a notch higher.

Successful therapy of plaque-type psoriasis with secukinumab in patients with multiple comorbidities treated with previous biologic therapies

Purpose: Biologic therapy in psoriatic patients with multiple comorbidities is challenging due to worsening of associated diseases and possible side effects of concomitant medications.Materials and methods: We describe three patients with multiple comorbidities documenting successful treatment of psoriasis with secukinumab following failure of multiple conventional and biologic DMARDs.Results: The first case is an obese 59-year-old woman (HBV + with latent tuberculosis) with arterial hypertension and 12-year history of breast cancer. The second is a 45-year-old obese man (HCV + with occult HBV infection on therapy with multiple antipsychotics and taking methadone for opioid dependence), while the last is a 39-year-old man with severe obesity, non-alcoholic hepatosteatosis, and NYHA class II heart failure. All three patients had undergone previous conventional (methotrexate, cyclosporine, retinoids, and phototherapy) and multiple biologic treatments (one or more of the following: adalimumab, ustekinumab, etanercept, infliximab originator, and biosimilar) that were discontinued for inefficacy and/or adverse effects. All patients underwent therapy with secukinumab, which was associated with sustained clinical benefits and no clinically relevant safety findings.Conclusions: The present three cases add further evidence that secukinumab is effective and well tolerated in difficult to treat psoriatic patients with multiple comorbidities, namely HBV, latent TBC infection, and hepatic impairment.

Treatment of patients with plaque psoriasis with secukinumab in a real-life setting: a 52-week, multicenter, retrospective study in Spain

Background: The efficacy and safety of secukinumab in patients with plaque psoriasis (PsO) have been demonstrated in randomized clinical trials (RCTs). However, data regarding its efficacy and safety in real-life settings are scarce.Objectives: To evaluate the efficacy and safety of secukinumab in clinical practice in patients with PsO attending 10 dermatology centers in Spain.Methods: Data from 136 patients consecutively treated with secukinumab for at least 52 weeks were collected in a retrospective observational study.Results: After 52 weeks of treatment, 69% and 46% of patients achieved a PASI-75, PASI-90, respectively. PASI-score ≤5 was achieved in 83% of patients, PASI-score ≤3 in 73% and PASI-score ≤1 in 47%. Response rates were found significantly lower in patients with obesity and non-naïve to biologics (p < .05). The most common adverse event (AE) was candidiasis (5/136). Thirty-six patients (26.5%) discontinued treatment by week 52 due to lack or loss of response (n = 29), AEs (n = 2) or other causes (n = 5).Conclusion: These findings complement the efficacy and safety profiles of secukinumab in PsO outlined in RCTs. The effectiveness in clinical practice may be lower in patients with a BMI ≥30 and those previously treated with other biologic agents.

PSS7 - QUALITY OF LIFE IMPROVEMENTS IN PSORIASIS WITH SECUKINUMAB IN A DIFFICULT TO TREAT POPULATION OF ANTI-TNF ALPHA FAILURE PATIENTS FROM THE UK AND REPUBLIC OF IRELAND

Psoriasis can have a large impact on quality of life (QoL). Secukinumab, a fully human anti–interleukin-17A monoclonal antibody is licensed for the treatment of plaque psoriasis in adults who are candidates for systemic therapy. QoL results are presented from an open-label, non-comparator study that investigated the safety and efficacy of secukinumab in patients who previously failed anti-tumour necrosis factor (TNF) α biologic therapy. 235 eligible adults with active, moderate-to-severe, chronic plaque psoriasis from 53 sites in UK and Ireland were randomised 1:1 to receive secukinumab 300mg or 150mg subcutaneously for 72 weeks (dosing at weeks 0-4, then 4-weekly). Patients completed the Dermatology Life Quality Index (DLQI, range 0-30, higher scores reflecting worse QoL) and EuroQoL 5-Dimension Health Status Questionnaire (EQ-5D-5L) at baseline, weeks 12, 16, 24, 48 and 72. Results are presented for 118 patients on the dose of secukinumab licensed for psoriasis (300mg). At baseline, mean DLQI was 20.2 (SD=6.03). By week 16 this improved to 4.2 (SD=4.97). Improvements were maintained amongst patients remaining in the study; 4.2 (SD=5.90) at week 48 and 3.7 (SD=5.41) at week 72. Baseline EQ-5D-5L mean visual analogue score (VAS; range 0-100, lower scores reflecting worse QoL) was 54.9 (SD=24.84). By week 16 this improved to 76.3 (SD=21.58). Improvements were maintained amongst patients remaining in the study; 77.7 (SD=21.60) at week 48 and 78.2 (SD=19.80) at week 72. EQ-5D domains impacting the largest proportion of patients at baseline were pain/discomfort (90%; 106/118 patients) and anxiety/depression (77%; 91/118). By weeks 16, 48 and 72 respectively, fewer patients were reporting pain/discomfort; 53% (63/118), 43% (46/107) and 52% (43/83) and anxiety/depression; 38% (45/118), 36% (39/107) and 37% (31/83). These results demonstrate that secukinumab 300mg provides sustained QoL improvements even in a difficult to treat anti-TNFa failure population of psoriasis patients.

Secukinumab in the treatment of psoriatic arthritis: efficacy and safety results through 3 years from the year 1 extension of the randomised phase III FUTURE 1 trial

ObjectiveTo assess the long-term (3 year) efficacy and safety of secukinumab in patients with active psoriatic arthritis (PsA) in the extension phase of the FUTURE 1 study (NCT01892436).MethodsFollowing the 2-year...

Cost-effectiveness analysis of sequential biologic therapy with ixekizumab versus secukinumab as first-line treatment of moderate-to-severe psoriasis in the UK

Aims: Patients with psoriasis often undergo treatment with a sequence of biologic agents because of poor/loss of response to initial therapy. With the availability of newer agents like ixekizumab and secukinumab, there is a need for cost-effectiveness analyses to better reflect current clinical practice. This study aimed to assess the cost-effectiveness of a sequence of biologic therapies containing first-line ixekizumab vs first-line secukinumab in patients with moderate-to-severe plaque psoriasis in the UK.Materials and methods: A Markov model with a lifetime horizon was developed to compare the cost-effectiveness of ixekizumab and secukinumab treatment sequences: ixekizumab → ustekinumab → infliximab → best supportive care (BSC) vs secukinumab → ustekinumab → infliximab → BSC. The model used monthly cycles, and included four health states: trial period, treatment maintenance, BSC, and death. At the end of the trial period, responders transitioned to maintenance therapy; non-responders transitioned to the next biologic in the sequence. An annual discontinuation rate of 20% was assumed for maintenance therapy.Results: The ixekizumab sequence provided cost savings of £898 (£176,203 vs 177,101) [year 2015 values] and gained 0.03 more quality-adjusted life-years (QALYs: 1.45 vs 1.42) vs the secukinumab sequence over the lifetime horizon. Probabilistic sensitivity analysis showed an 89.8% likelihood that the ixekizumab sequence would be cost-effective at a threshold of £20,000 per QALY gained.Limitations: The analysis used list prices for drugs rather than confidential, preferentially priced Patient Access Scheme costs. In addition, efficacy input data were based on a network meta-analysis, as there were no head-to-head trials comparing ixekizumab and secukinumab.Conclusion: First-line treatment with ixekizumab as part of a specific sequential biologic therapy for moderate-to-severe plaque psoriasis in the UK provided slight advantages in cost savings and QALYs gained over a similar treatment sequence initiated with secukinumab. In view of the small magnitude of these differences, factors such as patient preferences (e.g. for number of injections) and long-term safety (e.g. related to time on the market) may also be important for clinical decision-making.

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis

Objective: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors.Method: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years.Results: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies.Conclusions: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.

Initial Results of Secukinumab Drug Survival in Patients with Psoriasis: A Multicentre Daily Practice Cohort Study.

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice.

Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study.

Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus (HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.

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.