Inhibition of interleukin-17 in patients with oligoarticular psoriatic arthritis

Introduction: This study evaluated the efficacy of the interleukin-17A inhibitor secukinumab in patients with oligoarticular psoriatic arthritis (PsA). Methods: A total of 84 patients with oligoarticular PsA, defined as 1–4 tender joints and 1–4 swollen joints, were pooled from the FUTURE 2–5 and MAXIMISE trials (NCT01752634, NCT01989468, NCT02294227, NCT02404350, and NCT02721966). Patients were grouped by treatment received at week 12 (secukinumab 300 mg, secukinumab 150 mg, or placebo) and week 52 (any secukinumab 300 mg or any secukinumab 150 mg). Efficacy was assessed by the proportion of patients achieving selected clinical outcomes. The predictors of Disease Activity index for Psoriatic Arthritis (DAPSA) responses at weeks 12 and 52 were identified by logistic regression analysis. Results: Secukinumab treatment resulted in greater achievement of DAPSA-based low disease activity (LDA), DAPSA-based remission (REM), DAPSA50, and DAPSA75 than placebo at week 12, with improvements sustained or further increased through week 52. LDA or REM was achieved at week 52 by more than 90% of patients who received either secukinumab dose, although secukinumab 300 mg resulted in the highest achievement of the stringent DAPSA75 and DAPSA REM outcomes. At week 12, younger age was associated with DAPSA LDA or REM and DAPSA50, while lower baseline swollen joint count was associated with DAPSA REM. No predictors were identified at week 52. The safety profile was consistent with the full study populations. Conclusion: Secukinumab demonstrated efficacy vs placebo across several outcome measures in patients with oligoarticular PsA at week 12, with sustained or improved responses through week 52

Interim 2-year analysis from SERENA: A real-world study in patients with psoriatic arthritis or ankylosing spondylitis treated with secukinumab

Introduction: Sustained improvement of high degree in clinical outcomes have been demonstrated in phase 3 trials with secukinumab in both psoriatic arthritis (PsA) and ankylosing spondylitis (AS). The objective of the SERENA study was to evaluate the effectiveness, retention rates, and safety of secukinumab in patients with PsA and AS. Methods: SERENA is an ongoing, longitudinal, real-world observational study involving patients with moderate-to-severe psoriasis, PsA, or AS. Patients had received at least 16 weeks of secukinumab treatment before recruitment to the study. Retention rate was defined as percentage of patients who continued secukinumab treatment over the course of study. Effectiveness of secukinumab in AS and PsA cohorts was assessed using descriptive statistics. Results: The current interim analysis included 1004 patients with PsA or AS. Overall secukinumab retention rates at 2 years after enrolment were 74.9 and 78.9% in patients with PsA and AS, respectively. At baseline and at 2 years, swollen joint count [3.3 (5.8) vs. 2.9 (5.8)], tender joint count [6.3 (9.4) vs. 5.6 (7.2)] in patients with PsA and BASDAI scores [3.2 (2.3) vs. 2.9 (2.3)] in patients with AS, suggest sustained effectiveness for patients remaining on secukinumab for at least 2 years after enrolment. A total of 73 patients had treatment interruption; 78% of these patients reinitiated secukinumab without a loading dose. No new or unexpected safety signals were reported. Conclusions: After more than 2 years since initiation, secukinumab demonstrated high retention rates and favorable safety profile as well as sustained effectiveness in patients who continued secukinumab treatment

Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis

Objectives: Identify distinct clusters of psoriatic arthritis (PsA) patients based on their baseline articular, entheseal and cutaneous disease manifestations and explore their clinical and therapeutic value. Methods: Pooled baseline data in PsA patients (n=1894) treated with secukinumab across four phase 3 studies (FUTURE 2–5) were analysed to determine phenotypes based on clusters of clinical indicators. Finite mixture models methodology was applied to generate clinical clusters and mean longitudinal responses were compared between secukinumab doses (300 vs 150 mg) across identified clusters and clinical indicators through week 52 using machine learning (ML) techniques. Results: Seven distinct patient clusters were identified. Cluster 1 (very-high (VH) – SWO/TEN (swollen/tender); n=187) was characterised by VH polyarticular burden for both tenderness and swelling of joints, while cluster 2 (H (high) – TEN; n=251) was marked by high polyarticular burden in tender joints and cluster 3 (H – Feet – Dactylitis; n=175) by high burden in joints of feet and dactylitis. For cluster 4 (L (Low) – Nails – Skin; n=209), cluster 5 (L – skin; n=283), cluster 6 (L – Nails; n=294) and cluster 7 (L; n=495) articular burden was low but nail and skin involvement was variable, with cluster 7 marked by mild disease activity across all domains. Greater improvements in the longitudinal responses for enthesitis in cluster 2, enthesitis and Psoriasis Area and Severity Index (PASI) in cluster 4 and PASI in cluster 6 were shown for secukinumab 300 mg compared with 150 mg. Conclusions: PsA clusters identified by ML follow variable response trajectories indicating their potential to predict precise impact on patients’ outcomes. Trial registration numbers: NCT01752634, NCT01989468, NCT02294227, NCT02404350

Secukinumab use in patients with moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis in real-world setting in Europe: Baseline data from SERENA study

INTRODUCTION: Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. METHODS: SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. RESULTS: Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N = 460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m2) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89-1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n = 1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. CONCLUSION: Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting

Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients receiving secukinumab: a literature review

Purpose: There is a paucity of evidence on the impact of immune-mediated inflammatory disease (IMID) treatments on the immunogenicity of SARS-CoV-2 vaccination. The purpose of this literature review is to address the question of whether patients with IMIDs receiving secukinumab, a fully human anti-interleukin-17A monoclonal antibody, have an adequate immune response after SARS-CoV-2 vaccination. Materials and Methods: Clinical studies that evaluated the effect of secukinumab on immune responses in patients with IMIDs after SARS-CoV-2 vaccination were searched in publication databases, including Medline and Embase, until May 2022. Results: From the 53 articles identified, a total of 11 articles were included. Overall, the majority of the patients treated with secukinumab elicited an adequate immune response to SARS-CoV-2 vaccines. Patients receiving secukinumab for IMIDs developed cellular immune responses following vaccination with the BNT162b2 vaccine, and there were no significant differences in the overall humoral and cellular immune responses between patients and healthy individuals. The third dose of the BNT162b2 mRNA vaccine resulted in a positive antibody response in secukinumab-treated patients. Conclusion: The available data provide no evidence of impairment in immunological response to SARS-CoV-2 vaccines by secukinumab in patients with IMIDs

Inhibition of Interleukin-17 in Patients with Oligoarticular Psoriatic Arthritis.

INTRODUCTION: This study evaluated the efficacy of the interleukin-17A inhibitor secukinumab in patients with oligoarticular psoriatic arthritis (PsA). METHODS: A total of 84 patients with oligoarticular PsA, defined as 1-4 tender joints and 1-4 swollen joints, were pooled from the FUTURE 2-5 and MAXIMISE trials (NCT01752634, NCT01989468, NCT02294227, NCT02404350, and NCT02721966). Patients were grouped by treatment received at week 12 (secukinumab 300 mg, secukinumab 150 mg, or placebo) and week 52 (any secukinumab 300 mg or any secukinumab 150 mg). Efficacy was assessed by the proportion of patients achieving selected clinical outcomes. The predictors of Disease Activity index for Psoriatic Arthritis (DAPSA) responses at weeks 12 and 52 were identified by logistic regression analysis. RESULTS: Secukinumab treatment resulted in greater achievement of DAPSA-based low disease activity (LDA), DAPSA-based remission (REM), DAPSA50, and DAPSA75 than placebo at week 12, with improvements sustained or further increased through week 52. LDA or REM was achieved at week 52 by more than 90% of patients who received either secukinumab dose, although secukinumab 300 mg resulted in the highest achievement of the stringent DAPSA75 and DAPSA REM outcomes. At week 12, younger age was associated with DAPSA LDA or REM and DAPSA50, while lower baseline swollen joint count was associated with DAPSA REM. No predictors were identified at week 52. The safety profile was consistent with the full study populations. CONCLUSION: Secukinumab demonstrated efficacy vs placebo across several outcome measures in patients with oligoarticular PsA at week 12, with sustained or improved responses through week 52

Short Stature: Comparison of WHO and National Growth Standards/References for Height.

The use of appropriate growth standards/references is of significant clinical importance in assessing the height of children with short stature as it may determine eligibility for appropriate therapy. The aim of this study was to determine the impact of using World Health Organization (WHO) instead of national growth standards/references on height assessment in short children. Data were collected from routine clinical practice (1998-2014) from nine European countries that have available national growth references and were enrolled in NordiNet® International Outcome Study (IOS) (NCT00960128), a large-scale, non-interventional, multinational study. The patient cohort consisted of 5996 short pediatric patients diagnosed with growth hormone deficiency (GHD), Turner syndrome (TS) or born small for gestational age (SGA). The proportions of children with baseline height standard deviation score (SDS) below clinical cut-off values (-2 SDS for GHD and TS; -2.5 SDS for SGA) based on national growth references and WHO growth standards/references were compared for children aged <5 years and children aged ≥5 years. In seven of the countries evaluated, significantly fewer children aged ≥5 years with GHD (22%; P<0.0001), TS (21%; P<0.0001) or born SGA (32%; P<0.0001) had height below clinical cut-off values using WHO growth references vs. national references. Likewise, among children aged <5 years in the pooled analysis of the same seven countries, a significantly lower proportion of children with GHD (8%; P<0.0001), TS (12%; P = 0.0003) or born SGA (12%; P<0.0001) had height below clinical cut-off values using WHO growth standards vs. national references. In conclusion, in NordiNet® IOS the number of patients misclassified using WHO growth standards/references was significantly higher than with national references. This study highlights that, although no growth reference has 100% sensitivity for identifying growth disorders, the most recent national or regional growth charts may offer the most appropriate tool for monitoring childhood growth in Europe

Magnetic resonance imaging characteristics in patients with psoriatic arthritis and axial manifestations from the MAXIMISE cohort

Objective The current analysis of the MAXIMISE trial was conducted to investigate the presence of post-inflammatory and degenerative spinal changes and inflammatory changes in spinal processes identified in baseline MRIs and their potential for predicting differential treatment effects in a cohort of PsA patients with axial manifestations. Methods Baseline spinal MRIs from the MAXIMISE trial were re-read to identify additional inflammatory (spinal process), post-inflammatory, and degenerative changes, and investigate the differential treatment effect of these imaging features using logistic regression modelling. Results In addition to bone marrow oedema assessed at primary analysis, spinal process inflammation and post-inflammatory changes evaluated by FAt Spondyloarthritis Spine Score were documented in 11.1% and 20.2% patients, respectively. At least one type of degenerative change was noted in 64% patients, with Pfirrmann grade ≥3 (51.1%) being the most common. Combining primary and re-read MRI findings, 67.1% of patients presented with inflammatory or post-inflammatory changes while 21.2% had degenerative changes alone. Although not statistically significant, post-inflammatory changes were associated with a trend for better efficacy outcomes in terms of ASAS20, ASAS40 and BASDAI50 responses; a trend for worse outcomes was observed in the presence of degenerative changes. Conclusion The current analysis revealed the occurrence of additional inflammatory and post-inflammatory changes suggestive of axial PsA (axPsA) and a trend for better clinical outcomes for patients treated with secukinumab. These results elucidate the imaging characteristics and improve our current understanding of axPsA thereby supporting the interpretation of future trials.Funding. This study was supported by Novartis Pharma AG, Switzerland. Disclosure statement: X.B.: consultancy honoraria and research grants: AbbVie, BMS, Galapagos, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz and UCB; E.P.: employee of Novartis with Novartis stock; L.C.: grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Pfizer and Novartis; consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB; and speaker for AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer and UCB; R.B.: research grants: AbbVie, MSD and Roche; consulting fees: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma and MSD; speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD and Lilly; V.N.C.: research grants/honoraria from AbbVie, Galapagos, Janssen, Lilly, Moonlake, Novartis, Pfizer and UCB; E.O.: employee of Novartis; B.S.: was an employee of Novartis until manuscript submission and currently working as an employee of GKM Gesellschaft fuer Therapieforschung mbH; R.L.: research grants: AbbVie, Novartis, Pfizer and UCB; speakers bureau: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli-Lilly, Janssen, Gilead, Galapagos, Glaxo-Smith-Kline, Novartis, Pfizer and UCB. Patient consent for publication: Not required. Acknowledgements. The authors thank the patients and the study investigators who participated in this study. The authors also thank Andrew Franklin (Novartis Pharma AG, Basel, Switzerland) for the valuable review. Medical writing support, under the guidance of the authors, was provided by Dhanya Mukundan and Rajeeb Ghosh, Novartis Healthcare Private Limited, Hyderabad, India