interleukin-17A Inhibitor Research Articles

Experience in using secukinumab in patients with axial psoriatic arthritis

Axial skeletal injury is observed in 25–70% of patients with psoriatic arthritis (PsA). Spondylitis frequently occurs subclinically, which leads to serious structural and functional disorders over time. An update shows that axial skeleton involvement in PsA is characterized by a more severe clinical course: these patients are observed to have a greater severity of peripheral arthritis, enthesitis, and dactylitis, skin and nail psoriasis, a higher CRP level, and worse functional status. In addition, the disease is more severe according to the patients' subjective assessment, as evidenced by questionnaires. Synthetic disease-modifying antirheumatic drugs used to treat peripheral PsA are not recommended for axial injury. When nonsteroidal anti-inflammatory drugs are ineffective, biological drugs (tumor necrosis factor-α inhibitors or interleukin-17A (IL-17A) inhibitors) should be prescribed immediately to patients with psoriatic spondylitis. The paper describes two clinical cases demonstrating the successful use of the IL-17A inhibitor secukinumab (SEC) in patients with axial PsA (axPsA). Given the positive experience with SEC in real clinical practice, it seems reasonable to prescribe it to patients at earlier stages of axPsA.

Successful use of the interleukin-17A inhibitor (ixekizumab) in the treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic immune-mediated disease from a group of spondyloarthritis, which is characterized by damage to the musculoskeletal system with a wide range of different clinical manifestations and is usually associated with psoriasis. Activation of the interleukin (IL) 23/IL17 axis plays a key role in the pathogenesis of PsA and psoriasis. When non-steroidal and synthetic disease-modifying antirheumatic drugs are insufficiently effective, biological drugs are recommended. In recent years, there have been considerable advances in PsA treatment with tumor necrosis factor-α (IFN-α) inhibitors and IL-12/23 inhibitors. However, in some cases, this therapy fails to provide the desired effect and a search for new treatments for PsA seems to be an urgent task. The paper desctibes a clinical case demonstrating the efficacy of the IL17A inhibitor ixekizumab in a patient with high PsA activity and recurrent uveitis in both eyes. Ixekizumab therapy resulted in positive changes as the reduced severity of articular syndrome and psoriasis and normalization of acute phase parameters. Assessing the activity of PsA over time when using ixekizumab during a year showed an average decrease in ESR from 72 to 19 mm/h, in CRP from 162.1 to 0 mg/L, BSA from 51 to 0.25%, PASI from 43. 6 to 0, DAPSA from 78.2 to 2, ASDAS-SRB from 5.11 to 1.12, BASDAI from 4.85 to 1, BASFI from 5.3 to 0.7, BASMI from 5.0 to 2.6, MASES from 6 to 0, LEI from 2 to 0, SPARCC from 6 to 0, and NAPSI from 28 to 8. Thus, this clinical case is an example of successful treatment with the IL17 inhibitor ixekizumab for PsA with recurrent uveitis in the patient who has previously received three drugs from the TNFα group without any effect.

Brodalumab success in patients with moderate-to-severe psoriasis who failed previous interleukin-17A inhibitors

To the Editor: The interleukin-17 (IL17) signaling pathway plays a pivotal role in the pathogenesis of psoriasis. While several studies investigated the efficacy and safety of switching between IL17A inhibitors, data on switching from IL17A inhibitors to the IL17 receptor A (IL17RA) antagonist brodalumab remain limited.

Interleukin-17A biomarker as a predictor for detection of early axial spondyloarthritis changes in patients with psoriasis.

Although the pathogenic mechanisms of psoriatic arthritis (PsA) are not completely clarified, evidence suggests that interleukin 17A (IL-17A)-mediated immune responses play a pivotal role in the disease. This is best underscored by the important clinical effectiveness of IL-17A inhibitors in psoriasis treatment. We aim to investigate the predictive value of IL-17A in detecting the early axial spondyloarthropic (SpA) changes in psoriatic patients. The study enrolled 100 patients with psoriasis, classified into group 1, included 62 patients with only psoriatic skin lesions (Ps), and group 2 included 38 patients with PsA, and 100 age and gender matched healthy volunteers. All participants were subjected to general and local clinical examination, laboratory assessment including IL-17A in the serum by means of enzyme-linked immunosorbent assay, and axial joint radiological assessment. Our study included 60 males (60%) and 40 females (40%).The positive radiological findings of early axial SpA changes were found among 30.6% of the Ps group and among 84.2% of the PsA group. There were significant differences between patients with positive magnetic resonance imaging (MRI) findings of early axial SpA and patients with negative MRI findings in both groups regarding IL-17A levels. There was a significant association between IL-17A level and early axial SpA changes in psoriatic patients with a clear cutoff point (222.5). Our study can imply that IL-17A is a valuable, useful and low-cost biomarker in detecting early axial SpA changes in asymptomatic and nonradiographic axial SpA (nr-axial SpA) psoriatic patients that helps early management and prevent progressive axial involvement and disabilities.

FRI0270 ONE-YEAR EFFECTIVENESS, RETENTION RATE AND SAFETY OF SECUKINUMAB IN ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS: A REAL-LIFE MULTICENTRE STUDY

Background:Secukinumab (SEC) is the first interleukin-17A inhibitor showing efficacy in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in randomised trials, but real-life data are lacking.Objectives:In this prospective observational study, we evaluated the effectiveness and safety of SEC in patients with AS and PsA in a real-life setting.Methods:From September 2018 to September 2019, data were collected from 168 consecutive outpatients at baseline (T0) and at 6 (T6) and 12 months (T12) after starting SEC (39 AS, 23%; 129 PsA, 77%).Results:Significant improvement was seen at T6 and T12 for all clinical variables, including TJC, SJC, ESR, CRP, DAPSA, ASDAS-CRP, and BASDAI, as well as in patient-reported outcomes such as VAS-pain. By multivariable regression analysis, in AS patients high BASDAI at T0 correlated with diagnostic delay (R2=0.4; p=0.009) and peripheral joint involvement (R2=0.4; p=0.04). During follow-up, reduction of BASDAI positively correlated with high ESR (R2=0.65; p=0.04). ASDAS-CRP at T0 positively correlated with high ESR (R2=0.34; p=0.004). Reduction of ASDAS-CRP from T0 to T6 correlated with current smoking status (R2=0.42; p=0.0005). In PsA patients, reduction of DAPSA score from T0 to T12 negatively correlated with the presence of metabolic syndrome (R2=0.41; p= 0.0025). Retention rate showed good drug survival and an influence of female sex (Figure 1) in the survival curve in only AS patients, but no differences based on BMI, gender and lines of treatment were observed (Figure 2). SEC was well tolerated: Eleven patients discontinued treatment for non-severe adverse events.Conclusion:We demonstrated the effectiveness and safety of SEC in patients with AS and PsA in a real-life setting for the first time. No gender differences were observed; however, less clinical improvement was seen in smokers and in patients with metabolic syndrome

O19 Secukinumab-related gastrointestinal safety in PsA and AS

Abstract Background Secukinumab is a selective interleukin-17a inhibitor (anti-IL17) and an effective treatment option for psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Phase III study safety data indicate a possible risk of inflammatory bowel disease (IBD), a link which is biologically plausible as IL-17 is known to influence intestinal immunopathology. Real world data for secukinumab gastrointestinal safety are limited. We set out to describe the post-licensing experience of secukinumab in routine care, evaluating both baseline evaluation of pre-existing IBD as well as incident gastrointestinal adverse effects. Methods We undertook a retrospective cohort study. Ten centres from the South East of England participated. All records for patients commencing secukinumab at each centre between 2016-2019 were reviewed. A fully anonymised data collection form was used to collate patient information. Questions sought to answer whether IBD screening had occurred prior to secukinumab initiation. All gastrointestinal adverse events were reviewed. IBD-related adverse events after initiation were defined as: definite (biopsy confirmed, objective inflammation from biomarkers, clear temporal association, improvement on drug withdrawal), probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria). Results Data for 306 patients were available: 124 (40.5%) with AS and 182 (59.5%) with PsA. 106 (34.6%) of patients had documented assessment for IBD prior to initiation; 7 of which already had pre-existing diagnoses of IBD. 24 (7.8%) patients experienced gastrointestinal related adverse events after starting secukinumab; 18 of which were formally investigated for bowel disease due to symptoms. Amongst patients who developed gastrointestinal symptoms, 4 (1.3%) had definite, 7 (2.3%) probable and 13 (4.2%) possible IBD. Out of the 4 with definite IBD; all were AS patients, all stopped secukinumab, three had pre-existing IBD and one (0.3%) case of de-novo IBD required surgical management for an inflammatory perianal abscess. All 7 patients with probable IBD had symptom resolution on withdrawal of secukinumab. Of these, 4/7 were PsA and 3/7 were AS. For the 13 patients that fulfilled possible IBD criteria, symptoms resolved without intervention and continued secukinumab treatment. Conclusion Absolute rates of new IBD in patients starting secukinumab are low. In addition, a majority of patients developing new gastrointestinal symptoms did not develop objective evidence of IBD or stop therapy. However, our experience suggests that in people with pre-existing IBD the risk is much higher. Only one-third of patients had documented evidence of screening for IBD at baseline. Given that only one patient developed de-novo IBD in the cohort, our experience would not support the practice of pre-screening for IBD prior to starting anti-IL17 therapy. Further research to evaluate this would be wise to focus specifically on the characteristics of AS patients, stratifying IBD risk prior to anti-IL17 initiation. Disclosures I.A. Onac: Other; Education support to attend conference from Abbvie. C. Tacu: Honoraria; Novartis Pharmaceutical UK - Speaker Fee. Other; education support- course - Novartis. B.D. Clarke: None. M. Lloyd: Other; departmental support from Novartis. V. Hajela: None. T. Batty: None. J. Thoroughgood: None. S. Smith: None. H. Irvine: None. D. Hill: None. G. Baxter: None. N. Horwood: Other; attend conferences from Lilly and Abbvie. S. Mahendrakar: Other; Education support to attend conferences from Lilly. R. Rajak: Honoraria; Honoraria for speaker: Eli Lilly, Amgen, Internis, Roche, UCB, Abbvie. Honoraria for chairing: Roche, Novartis, Eli Lilly, UCB. S. Griffith: Other; None declared. P. Kiely: Honoraria; Abbvie, BMS, Gilead, Lilly, Novartis, Sanofi. Member of speakers’ bureau; Abbvie, BMS, Lilly, Novartis, Sanofi. J.B. Galloway: Honoraria; Speaker fees, travel support and grants from Lilly, Abbvie, BMS, Celgene, Janssen, Pfizer, UCB, Sanofi.

Long-term efficacy and safety of secukinumab in patients with psoriatic arthritis: 5-year (end-of-study) results from the phase 3 FUTURE 2 study.

Secukinumab is an interleukin-17A inhibitor used in the treatment of patients with active psoriatic arthritis. In the phase 3 FUTURE 2 trial, secukinumab showed sustained improvement in clinical outcomes over 2 years. Because scarce data exists on the long-term treatment with biological therapies in patients with psoriatic arthritis, we aimed to assess and describe the 5-year (end-of-study) results on the efficacy and safety of secukinumab 300 mg and 150 mg doses, as well as dose escalation, from the FUTURE 2 study. FUTURE 2 is a phase 3, double-blind, placebo-controlled study done at 76 centres in Asia, Australia, Canada, Europe, and the USA. Patients with active psoriatic arthritis aged 18 years or older were randomly assigned to either secukinumab (300 mg, 150 mg, or 75 mg) or placebo weekly from baseline and then every 4 weeks from week 4. Secukinumab dose was escalated from 150 mg to 300 mg and from 75 mg to 150 mg or 300 mg starting at week 128, if active signs of disease were observed in patients, on the basis of the physician's assessment, with the escalated dose maintained thereafter. We assessed key efficacy endpoints at week 260 (5 years) for secukinumab 300 mg and 150 mg, including American College of Rheumatology (ACR) and Psoriasis Area and Severity Index (PASI) responses. The safety analysis included all patients who received one or more doses of secukinumab. We report data as observed. This study is registered with ClinicalTrials.gov, NCT01752634. At randomisation, 65% of patients were naive to tumour necrosis factor inhibitors and 47% were receiving concomitant methotrexate. Of 397 patients randomly assigned in FUTURE 2, 248 (62%) completed 5 years of treatment, including 64 (64%) of 100 patients in the original secukinumab 300 mg group, 65 (65%) of 100 in the 150 mg group, 59 (60%) of 99 in the 75 mg group, and 60 (61%) of 98 in the placebo group. Overall, 127 (52%) of 242 patients required dose escalation during the study. ACR responses at 5 years were 71 (74%; ACR20), 50 (52%; ACR50), and 31 (32%; ACR70) of 96 evaluable patients in the secukinumab 300 mg group, and 67 (70%; ACR20), 41 (43%; ACR50), and 28 (29%; ACR70) of 96 evaluable patients in the secukinumab 150 mg group. From 24 to 32 weeks and from 48 to 84 weeks after dose escalation from secukinumab 150 mg to 300 mg, the proportions of ACR and PASI non-responders decreased, whereas the proportions of ACR and PASI responders increased. During the entire treatment period, the most frequent treatment-emergent serious adverse event was serious infection (exposure-adjusted incidence 1·7, 95% CI 1·1-2·5; n=25) in the any secukinumab group. No new or unexpected safety signals were reported. Secukinumab 300 mg and 150 mg provided sustained improvement in the signs and symptoms of psoriatic arthritis, with consistent safety over 5 years. This study supports the clinical benefit and safety of long-term treatment with secukinumab in patients with psoriatic arthritis. Novartis.

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review.

We aimed to perform a structured literature review of spinal radiographic progression, as assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), in patients with ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) treated with biologic therapy. Searches were limited to English language manuscripts published in the 11 years prior to 9 July 2019. Randomized controlled trials, open-label extensions (OLEs) and observational studies reporting mSASSS progression in patients with AS or nr-axSpA treated with biologics were eligible for inclusion. Bias was assessed using the methodological index for nonrandomized studies (MINORS) tool. Among the 322 studies identified in the literature search, 23 (11 OLEs and 12 cohort studies) met the eligibility criteria and were selected for inclusion. Most studies reported mSASSS progression in patients with AS receiving tumor necrosis factor inhibitor (TNFi) treatment. One study reported mSASSS progression in patients with AS treated with secukinumab, an interleukin-17A inhibitor. The mean (range) MINORS score was 11.3 (7–15) for the 15 noncomparative studies and 15 (12–22) for the 8 comparative studies. Although results of the individual studies were variable, mSASSS progression in patients with AS was generally minimal and slow with long-term TNFi therapy. Moreover, odds ratios for the likelihood of mSASSS progression with/without TNFi favoured TNFi therapy in several of the cohort studies. The rate of mSASSS progression following continuous secukinumab treatment was low and remained stable over 4 years. Of two studies reporting progression in patients with nr-axSpA treated with TNFis, one showed no mSASSS progression; however, the lack of control limited comparative conclusions.

Management of ankylosing spondylitis; present concepts and guidelines

Ankylosing spondylitis (AS) belongs to spondyloarthritis (SpA) group of inflammatory arthritis, which has common genetic, clinical, and radiological features. The management aims at improving the quality of life, long-term control of inflammation so as to prevent structural damage, preserve functional abilities, and maintain the social life of patients. Treatment strategies and modalities in inflammatory arthritis have tremendously improved in recent times. With the discovery of molecular mechanisms, a new series of targets involving the cytokines, cells, and intracellular signaling pathways have been explored. The introduction of tumor necrosis factor inhibitor drugs heralded a new era of therapeutics for SpA, especially AS. Recently, the licensing of secukinumab, an interleukin 17A inhibitor for the treatment of AS, has given a new pathway to look at. These new targets give us an opportunity to achieve disease remission in both AS and nonradiologic axial SpA. They have also opened up new horizon to look for different research strategies in achieving disease remission using biological drugs in early disease and in stratified manner. International societies have been regularly providing and updating the guidelines for the management of AS. In this review, we discuss the treatment of AS and future trends in the management.

A Case of Widespread Dermatophytosis during Interleukin-17A Inhibitor Treatment in Psoriasis Patient with Tinea Unguium

Interleukin-17 (IL-17) is secreted by a class of helper T cells called Th17 cells, which stimulates keratinocytes to secrete proinflammatory mediator and to recruit other inflammatory cells in psoriatic skins. IL-17A inhibitor was approved for the management of psoriatic arthritis by FDA. It is the one of the biologics approved as first-line therapy for the management of psoriasis. But several studies show some side effects of IL-17A inhibitor such as upper respiratory infection and fungal infection like Candida albicans. Herein we report a widespread dermatophytosis during IL-17A inhibitor treatment. A 66-year-old male patient, with tinea unguium and chronic plaque psoriasis for several decades, presented with multiple erythematous scaly macules and patches for 2 weeks. He medicated IL-17A inhibitor for treating psoriasis total 3 times and last injection was 1 week ago. Dermatological examination revealed the involvement of 20% body surface area in the form of erythematous scaly macules and patches. KOH mount revealed the presence of numerous hyphae. The patient was started on oral terbinafine, topical isoconazole and efinaconazole. His skin lesions were improved after 1 month of anti-fungal therapy. IL-17 plays an important role in mucocutaneous microbial defense. So, fungal infection should be checked in using IL-17A inhibitor patients periodically.

Efficacy and safety of a new original interleukin 17A inhibitor in the treatment of patients with active ankylosing spondylitis: results of a basic (BCD-085-3/AILAS) and extended (BCD-085-3ext/AILAS-II) phase II clinical trial

The paper presents the results of a double-blind (BCD-085-3/AILAS) phase II clinical trial of the original interleukin 17A (IL17A) inhibitor BCD-085 prescribed at different doses to patients with active ankylosing spondylitis (AS) and those of an extended (BCD-085-3ext/AILAS-II) trial characterizing the efficacy and safety of this drug when used for a year. The objective of the AILAS study is to determine the therapeutically effective and safe dose of BCD-085 in the treatment of active AS. The efficacy, safety, and immunogenicity of BCD-085 during its annual use were additionally evaluated in the extended trial. Subjects and methods . The investigation enrolled 89 patients diagnosed as having active (BASDAI scores >4.0; mean spinal pain scores >4.0) AS that met the 1984 New York classification criteria. After the end of the screening period, the patients were randomized at a ratio of 1:1:1:1 in one of four groups that received 40; 80 or 120 mg of BCD-085 subcutaneously or placebo on day 1 of weeks 0, 1, 2 and then once every two weeks up to week 12. The primary end point was the number of patients who achieved an ASAS20 response at week 16. The investigation evaluated the safety of the drug, by calculating the total incidence of adverse events (AEs) and serious AEs (SAEs) and the number of cases of premature therapy termination because of AEs. Results and discussion . An ASAS20 response at week 16 was achieved in 72.7% of patients receiving 40 mg of BCD-085, in 81.8% of those receiving 80 mg, in 90.9% of those receiving 120 mg, and in 42.9% of cases in the placebo group (p=0.004). The superiority of BCD-085 over placebo was proven for 80- and 120-mg doses. The fastest and most pronounced effect was observed in patients treated with 120 mg of BCD-085. In the extended study, an ASAS20 response at week 52 was recorded in 86.4% of patients. One or more AEs during the first 16 weeks of therapy were reported in 11 (50.0%) patients of the 40-mg group; in 6 (27.3%) of the 80 mg group; in 4 (18.2%) of the 120 mg group and in 7 (31.8%) of the placebo group (p=0.183). The frequency and spectrum of AEs did not significantly differ in patients who received placebo and BCD-085 in different doses. No SAE was recorded. Conclusion. Phase II study yielded data demonstrating the high efficacy and good tolerance of BCD-085 in the treatment of active AS. The best effect and optimal tolerance were demonstrated for a dose of 120 mg.

Comparison of real-world treatment patterns among patients with psoriasis prescribed ixekizumab or secukinumab

Real-world data on treatment patterns associated with use of interleukin-17A inhibitors in psoriasis are lacking. To compare treatment patterns between ixekizumab or secukinumab users in clinical practice. A retrospective cohort study included patients with psoriasis aged ≥18years treated with ixekizumab or secukinumab between March 1, 2016, and May 31, 2018 in IBM MarketScan (IBM Corp, Armonk, NY) databases. Inverse probability of treatment weighting and multivariable models were used to address cohort imbalances and estimate the risks of nonpersistence (60-day gap), discontinuation (≥90-day gap), switching, and the odds of adherence. The study monitored 645 ixekizumab users for 13.7months and 1152 secukinumab users for 16.3months. Ixekizumab users showed higher persistence rate (54.8% vs 45.1%, P<.001) and lower discontinuation rate (37.8% vs 47.5%, P<.001) than secukinumab. After multivariable adjustment, ixekizumab users had lower risks of nonpersistence (hazard ratio, 0.82; 95% confidence interval, 0.71-0.95) and discontinuation (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96), and higher odds of high adherence to treatment measured by a medication possession ratio ≥80% (hazard ratio, 1.31; 95% confidence interval, 1.07-1.60). The risk of switching was similar between cohorts. Disease severity and clinical outcomes were unavailable. Ixekizumab users demonstrated longer drug persistence, lower discontinuation rate and risk of discontinuation, higher likelihood of adherence, and similar risk of switching compared with secukinumab users in clinical practices.

Onset of Inflammatory Bowel Disease Following Interleukin-17A Inhibitor Treatment.

Onset of Inflammatory Bowel Disease Following Interleukin-17A Inhibitor Treatment.

PBI14 COST-EFFECTIVENESS OF SECUKINUMAB VERSUS OTHER BIOLOGICS AND APREMILAST IN THE TREATMENT OF ACTIVE PSORIATIC ARTHRITIS: A SPANISH PERSPECTIVE

To assess the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, with other biologics and apremilast in psoriatic arthritis (PsA) patients from a Spanish payers’ perspective. Secukinumab 150 mg and 300 mg were evaluated against etanercept, certolizumab pegol, adalimumab, golimumab, ustekinumab, infliximab, and apremilast over a lifetime horizon in a semi-Markov model. Both biologic-naïve (with or without moderate to severe psoriasis) and biologic-experienced PsA patients were considered. To assess treatment response, the 12-week PsA Response Criteria (PsARC) was used as a primary criterion. Model inputs were derived from PsA clinical trials, published literature, and other Spanish sources. Quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio were key model outcomes. Impact of input variations were evaluated through sensitivity analyses and alternative scenario analyses. Secukinumab 150 mg dominated all subcutaneous (S.C.) biologics and apremilast with highest QALYs of 9.22 and lowest lifetime cost of €192,445, while it was cost-effective against the intravenous (I.V.) infliximab in biologic-naïve patients without psoriasis. Among biologic-naïve patients with psoriasis and biologic-experienced patients, secukinumab 300 mg was cost-effective against all S.C. branded biologics and apremilast, while it dominated I.V. infliximab. PsARC response at 3-months, drug acquisition costs, and Health Assessment Questionnaire score change were identified as the most important parameters affecting model results as per one-way sensitivity analysis. Probabilistic sensitivity analysis showed maximum net monetary benefits with both secukinumab doses. Results from scenario analyses confirmed these results. Secukinumab is a cost-effective biologic treatment for PsA patients from a Spanish payer’s perspective.

The safety and optimal dosage of an interleukin-17A inhibitor (secukinumab) in the treatment of psoriatic arthritis in a patient with concomitant hepatitis C virus infection

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the group of spondylitides, which is associated with psoriasis. The decisive role is played by the activation of the interleukin (IL)-23/IL-17 axis in the pathogenesis of PsA [1]. Secukinumab (SEC) is a fully human antibody that binds to human IL-17A and neutralizes the activity of this cytokine. That the patient has concomitant diseases, chronic hepatitis B virus infection and hepatitis C viral (HCV) infection in particular, limits the use of tumor necrosis factor- α inhibitors in the treatment of PsA [2, 3]. The paper describes a clinical case that demonstrates the successful treatment with SEC in a patient with PsA and concomitant HCV infection. In addition to the safety aspects of the use of SEC to treat chronic HCV infection, the issues on optimal dosing of the drug are discussed.

Cost-Effectiveness of Secukinumab Versus Other Biologics in the Treatment of Psoriatic Arthritis: An Argentinean Perspective

ObjectivePsoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. This study assessed the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, versus other biologics in PsA from the Argentinean social security perspective. MethodsA semi-Markov model evaluated subcutaneous (sc) treatment with secukinumab 150 mg and 300 mg against other sc treatments such as adalimumab, certolizumab pegol, etanercept, golimumab, ustekinumab, and intravenous treatment infliximab in biologic-naïve (with or without moderate to severe psoriasis) and biologic-experienced PsA patients over a lifetime horizon. Response to treatments was determined using the PsA Response Criteria (PsARC) at 12 weeks. Model inputs were derived from randomized controlled trials, network meta-analyses, published literature, and other Argentinean sources. Model outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratios. Sensitivity analyses and alternative scenarios with a higher cost option were also conducted. ResultsAmong biologic-naïve PsA patients without psoriasis, secukinumab 150 mg provided the highest QALYs (7.18) versus all sc biologics at the lowest cost ($3 755 678 Argentine peso), thus dominating them. Among biologic-naïve PsA patients with psoriasis and biologic-experienced PsA patients, secukinumab 300 mg provided highest QALYs (6.99 and 7.53, respectively), dominated infliximab, and was cost-effective versus other sc biologics. Deterministic sensitivity analyses indicated sensitivity of results to variation in PsARC rates, drug acquisition costs, Health Assessment Questionnaire change, and utilities. A probabilistic sensitivity analysis showed maximum net monetary benefits with both secukinumab doses. Results from an alternative scenario analysis were similar to base-case analysis. ConclusionsFor both biologic-naïve and experienced PsA patients, secukinumab is either a dominant or cost-effective treatment option compared with other biologics in Argentina.

IL-17A Inhibitor Switching - Efficacy of Ixekizumab Following Secukinumab Failure. A Single-center Experience.

Interleukin-17A inhibitors are a promising alternative to tumor necrosis factor-α inhibitors for the treatment of psoriasis. In-class switch has been hardly investigated for interleukin-17A inhibitors. We report the experience (2017-2018) of a tertiary medical center with interleukin-17A-inhibitor switch in patients with moderate-to-severe psoriasis. Patient-, disease- and outcome-related data were retrospectively collected from the electronic files of 25 patients switched to ixekizumab following secukinumab failure. Mean ± standard deviation patient age was 56.7 ± 12.2 years. Mean baseline Psoriasis Area and Severity Index was 25. Secukinumab was discontinued due to primary failure in 7 patients and secondary failure in 18. Ixekizumab was administered for 7.3 ± 2.8 months; 22 patients were still on ixekizumab at the end of the study. Mean ± standard deviation Psoriasis Area and Severity Index reduction from baseline at study end was 75.5±20.0%. Patients with moderate-to-severe psoriasis seem to be amenable to treatment with ixekizumab following secukinumab failure. Further large multicenter studies are needed.

Demographics and disease burden of patients on interleukin-17A inhibitors compared with other biologics: Data from the Corrona Psoriasis Registry

Demographics and disease burden of patients on interleukin-17A inhibitors compared with other biologics: Data from the Corrona Psoriasis Registry

Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study

BackgroundAlthough the effects of interleukin-17A (IL-17A) inhibition on the signs and symptoms of psoriatic arthritis (PsA) are well defined, little is known about its impact of local inflammatory and structural changes in the joints. The PSARTROS study was designed to elucidate the effects of IL-17A inhibition on inflammation and bone changes in joints affected by PsA.MethodsThis was a prospective open-label study in 20 patients with active PsA receiving 24 weeks of treatment with the IL-17A inhibitor secukinumab. Magnetic resonance imaging (MRI), power Doppler ultrasound (PDUS), and high-resolution peripheral quantitative computer tomography (HR-pQCT) of the hands were performed at baseline and after 24 weeks to assess synovitis, periarticular inflammation, bone erosion, enthesiophyte formation, and bone structure. Demographic and clinical measures of joint disease (DAPSA and DAS28-ESR), skin disease (PASI and BSA), and composite measures (minimal disease activity, or MDA) were also recorded.ResultsTreatment with secukinumab led to significant improvement of signs and symptoms of PsA; 46% reached MDA and 52% DAPSA low disease activity. MRI synovitis (P = 0.034) and signal in PDUS (P = 0.030) significantly decreased after 24 weeks of treatment. Bone erosions in MRI and HR-pQCT and enthesiophytes in the HR-pQCT did not show any progression, and structural integrity and functional bone strength remained stable.ConclusionsIL-17 inhibition by secukinumab over 24 weeks led to a significant decrease of synovial inflammation and no progression of catabolic and anabolic bone changes in the joints of patients with PsA.Trial registrationClinicalTrials.gov Identifier: NCT02483234, June 26, 2015; retrospectively registered.

Effects of tumor necrosis factor-α, interleukin-23 and interleukin-17A inhibitors on bodyweight and body mass index in patients with psoriasis.

Treatment with tumor necrosis factor-α inhibitors has been reported to cause weight gain in patients with psoriasis; however, limited information is available in terms of the effects of interleukin (IL)-23 and IL-17A inhibitors on bodyweight (BW) in patients with psoriasis. This study aimed to investigate the effects of infliximab, ustekinumab and secukinumab on BW and body mass index (BMI) in patients with psoriasis. We retrospectively examined changes in BW and BMI among patients treated with these biologics at our hospital. At baseline, no significant differences in BW and BMI were observed among the patients treated with infliximab (n = 18), ustekinumab (n = 30) or secukinumab (n = 20). After 7 months of the therapy, significant increases in mean BW (from 71.4 to 74.3 kg) and mean BMI (from 24.7 to 25.7) were observed in the patients treated with infliximab, whereas no significant changes were observed in those treated with ustekinumab (BW, from 70.3 to 70.1 kg; BMI, from 25.4 to 25.3) or secukinumab (BW, from 69.0 to 68.9 kg; BMI, from 25.2 to 25.2). There were no differences in the proportion of the patients who showed 75% or more improvement in the Psoriasis Area and Severity Index among the three groups. These results suggest that infliximab increases BW in the patients with psoriasis, whereas ustekinumab and secukinumab do not affect the BW in these patients.