Psoriatic Arthritis Response Criteria Research Articles

Multi-domain effectiveness of guselkumab evaluated via composite indices through 1 year in patients with PsA and inadequate response to TNFi: post hoc analysis of COSMOS.

Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1-2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains. In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this post-hoc analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA) and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data. Greater proportions of guselkumab- than placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA; 14.8-52.4% vs 3.1-28.1%) or remission (3.7-5.3% vs 0.0-2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%; DAS28, 47.8%; PASDAS, 34.4%; GRACE, 33.3%; mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo→guselkumab crossover group, W48 response rates were similar to the guselkumab-randomized group. Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.

Bipolar androgen therapy for treatment of metastatic castration‐resistant prostate cancer: A case series

AbstractIntroductionAdvanced prostate cancer treatment has improved with androgen receptor signaling inhibitors (ARPI), yet many patients develop metastatic castration‐resistant prostate cancer (mCRPC), characterized by sustained androgen receptor (AR) signaling. Bipolar androgen therapy (BAT) introduces supraphysiologic testosterone levels to inhibit tumor growth, offering novel treatment for mCRPC by exploiting AR‐dependent mechanisms.Case PresentationsCase 1: A 53‐year‐old man with mCRPC, post multiple systemic therapies, initiated BAT and pembrolizumab, achieving PSA reduction and improved quality of life before progression. The patient exhibited AR amplification, which may have contributed to favorable response to BAT.Case 2: A 73‐year‐old man with recurrent prostate cancer, stable on ADT and abiraterone, experienced PSA decline with BAT to an undetectable level, maintaining stability post‐therapy discontinuation.Case 3: A 73‐year‐old man with metastatic prostate cancer, initially resistant to enzalutamide, achieved clinical benefit and disease control with BAT, although he did not meet PSA response criteria, patient had remarkable response upon enzalutamide rechallenge.Case 4: A 90‐year‐old man with localized prostate cancer, refractory to multiple treatments, experienced symptom relief and PSA reduction with BAT before progression.ConclusionBAT represents a promising treatment strategy for mCRPC. This case series underscores BAT's potential to induce significant clinical and biochemical responses, resensitize tumors to ARPIs, and improve patients' quality of life. Despite eventual progression in some cases, BAT offers a period of disease control. Further research is needed to optimize patient selection and understand the molecular determinants of BAT responsiveness.

P014 Treatment response in psoriatic arthritis: a comparison between the disease activity scores psoriatic arthritis response criteria and disease activity score-28

Abstract Background/Aims Despite NICE guidelines recommending the use of the PsA response criteria (PsARC), to assess response to biologic therapies in patients with psoriatic arthritis (PsA), some clinicians use the Disease Activity Score (DAS-28) criteria, developed for rheumatoid arthritis. However, whether the two scores are interchangeable and/or capture similar information has not yet been explored. Here, we investigate the differences and overlap between these two disease activity scores, in identifying good/poor responders, in PsA. Methods Utilising treatment response data from the OUTPASS cohort; a UK based multi-centre observational study, PsA patients assessed with PsARC and DAS-28 scores were calculated at baseline (pre-treatment), 3-months and 6-months (3M),(6M), following treatment, where available. EULAR good/moderate response was combined and compared with PsARC responder status. Subgroup analysis of patients with both PsARC and DAS-28 scores at either 3M or 6M, were tested for agreement using the Cohen’s Kappa test. Statistical tests were also used, as appropriate, to investigate differences between the baseline subcomponents, in the observed concordant and discordant data. Results Response data from 418 patients was available. An average of 76% were classified as responders according to PsARC, and 80% according to the EULAR response criteria, for both 3M and 6M, with 12% discordance. A subgroup analysis of 218 patients assessed with both scores, (up to 6M), revealed 17.9% responder discordance between PSARC and DAS-28, and 82.1% concordance. The Cohen’s Kappa test defined the assessment of responder/non-responder outcome, as an ‘almost perfect agreement’ (0.82) between the two criteria. Further statistical analyses, of baseline subcomponents, of both response criteria, between these discordant/concordant subsets, showed no significant difference, except for PsARC Physician’s and Patient’s Global Assessments (PhGA), (PGA), (P = 0.01, P = 0.02, Table 1). Conclusion PsARC and EULAR response criteria show ‘almost perfect agreement’, strongly supporting clinical use for either score. PhGA, (not a subcomponent of DAS-28) and PsARC PGA were the only significantly different (P < 0.05) components between the discordant and concordant groups, highlighting the importance of considering psychosocial factors which may affect pain tolerance and treatment response. Comparative analyses with other widely used scores, such as DAPSA, would also be informative for future work. Disclosure K. Patel: Grants/research support; This project has received support from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101007757 (HIPPOCRATES), the JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA, the results reflect only the author's view and the JU are not responsible for any use that may be made of the information it contains.. N. Nair: None. M. Jani: None. H. Chinoy: Consultancies; H.C. has received Consulting for PTC Therapeutics. Member of speakers’ bureau; H.C. has received fees as a speaker for GSK, UCB. Other; H.C. for Advisory Board member for Astra Zeneca, Pfizer, Argenx, Galapagos; Data and Science Monitoring Board chair for Horizon Therapeutics. J. Bluett: Grants/research support; J.B. has received a research grant award from Pfizer and travel/conference fees from UCB, Fresenius Kabi, Pfizer and Eli Lilly. (Pfizer: WI239449). A. Barton: Grants/research support; A.B. has received research grants from Bristol Myers Squibb and Pfizer and speaker fees from Galapagos.. P. Curry: None.

E070 Sustained and consistent efficacy of bimekizumab in patients with active psoriatic arthritis regardless of prior TNF-inhibitor status: results from the phase 3 BE OPTIMAL and BE COMPLETE trials

Abstract Background/Aims Bimekizumab (BKZ), a humanised monoclonal IgG1 antibody that inhibits IL-17A and IL-17F, has demonstrated rapid efficacy in joint and skin outcomes for patients with active psoriatic arthritis (PsA) who are bDMARD-naïve (BE OPTIMAL; NCT03895203) and TNFi-inadequate responders (TNFi-IR) (BE COMPLETE; NCT03896581). Here we report longer-term PsA response criteria (PsARC) response, along with health-related quality of life (HRQoL) outcomes in BE OPTIMAL and BE COMPLETE. Methods BE OPTIMAL and BE COMPLETE were randomised multicentre, double-blind, placebo (PBO)-controlled, parallel-group, phase 3 trials. BE OPTIMAL included a 16-week (Wk) double-blind, PBO-controlled period and a 36-Wk active-treatment period. Patients were randomised (3:2) to receive BKZ 160mg Q4W, or PBO. At Wk16, PBO patients switched to BKZ. In BE COMPLETE, patients with inadequate response or intolerance to TNFis were randomised (2:1) to receive either BKZ 160mg Q4W or PBO for 16Wks after which they were eligible for entry into BE VITAL (NCT04009499; open-label extension). We report PsARC response rates at Wk52 (BE OPTIMAL) and Wk40 (BE COMPLETE). Additionally, the association of PsARC responders with HRQoL-related outcomes (HAQ-DI, FACIT-Fatigue and SF-36) for the randomised set are also reported. Data are reported as non-responder imputation (NRI) and observed cases (OC). Results In BE OPTIMAL, 821/852 (96.4%) patients completed Wk16 and 761 (89.3%) completed Wk52. In BE COMPLETE, 388/400 (97%) patients completed Wk16, 377 (94.3%) entered BE VITAL and 360 (90.0%) completed Wk40. Baseline characteristics were comparable between groups within both trials. In BE OPTIMAL, PsARC response (NRI) was achieved by 80.3% BKZ and 40.2% PBO patients at Wk16 and was sustained or increased at Wk52 to 79.1% BKZ and 79.7% PBO/BKZ patients. In BE COMPLETE, PsARC response (NRI) was achieved by 85.4% BKZ and 30.8% PBO at Wk16 and was sustained or increased at Wk40 to 77.9% BKZ and 75.2% PBO/BKZ patients. Clinically meaningful improvements in HAQ-DI and SF 36-PCS scores, and FACIT-Fatigue were achieved from baseline among PsARC responders compared to non-responders (Table). Conclusion Improvements in PsARC were sustained up to 1 year in BKZ-treated patients and associated with improvement in HRQoL and fatigue, regardless of whether patients were bDMARD-naïve (BE OPTIMAL) or TNFi-IR (BE COMPLETE). Disclosure W.R. Tillett: Other; WRT has received Research funding, consulting and or speaker fees from: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. B. Ink: Shareholder/stock ownership; BI is a shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. R. Bajracharya: Other; RB is an employee and shareholder of UCB Pharma. V. Taieb: Other; VT is an employee of UCB Pharma. P. Sharma: Other; PS has done Advisory Board for UCB Pharma. D. McGonagle: Grants/research support; DM has received research grants/research support from AbbVie, Celgene, Janssen, Merck, and, Pfizer. Other; DM has received honoraria or consultation fees and has been paid as a speaker for AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer, and UCB Pharma. L.C. Coates: Consultancies; LCC has worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB Pharma. Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. Other; LCC has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB Pharma. I.B. McInnes: Grants/research support; IM has received grants/research support from Astra Zeneca, Abbvie, BMS, Compugen, Cabaletta, EveloBio, Eli Lilly, GSK, Janssen, Novartis, Moonlake, Novartis, Sanofi, UCB Pharma, XinThera.

Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response.

The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (ΔDAS28) between baseline and 3, 6 and 12 months. In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater ΔDAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and ΔDAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures.

P189 Bimekizumab in patients with psoriatic arthritis with prior inadequate response to TNF inhibitors: improvements of PsARC over 16 weeks in the Phase 3 BE COMPLETE trial

Abstract Background/Aims Bimekizumab (BKZ) is a humanised monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A and has demonstrated clinical effectiveness in both joint and skin outcomes in patients with active psoriatic arthritis (PsA). Psoriatic Arthritis Response Criteria (PsARC) is used routinely for drug reimbursement in clinical practice in the UK. We report PsARC response rates along with HRQoL estimates at week (wk) 16 in TNF inadequate responder (TNFi-IR) patients with active PsA from the phase 3, 16-wk BE COMPLETE trial (NCT03896581). Methods BE COMPLETE is a randomised, multicentre, double-blind, placebo (PBO)-controlled, parallel group study. Patients who had an inadequate response or intolerance to treatment with 1 or 2 TNFis were randomised (2:1) to BKZ 160 mg every 4 wks (Q4W) or PBO for 16 wk. We report response rates for PsARC at wk 16, and the association of PsARC responders with HRQoL-related outcomes for the randomised set. Data are reported as non-responder imputation (NRI) and observed cases. Results 400 patients were randomised at baseline (BKZ: 267; PBO: 133). Baseline characteristics were comparable between groups (mean age: 50.5 yrs; BMI: 29.8 kg/m2; disease duration: 9.5 yrs and 47.5% were male). At wk 16, PsARC response (NRI) was achieved by 85.4% with BKZ and 30.8% with PBO (Table). Numerically greater improvements in physical functioning and fatigue measure were achieved from baseline among PsARC responders compared to non-responders (Table). Over 16 wks, safety was in line with previous BKZ studies and no new safety signals were observed. Conclusion In patients with prior TNFi-IR with active PsA, BKZ treatment demonstrated a greater improvement in musculoskeletal symptoms at wk 16 compared to PBO. Patients with PsARC response had numerically greater improvements in HRQoL and improvements in fatigue measures. No new safety signals were observed. Disclosure P. Sharma: Other; PS has received conference sponsorship Amgen 2015 for National Osteoporosis Conference; Janssen Advisory Board board Nov 22. D.R. Jadon: Other; DRJ received research/education grants/honoraria: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Fresenius Kabi, Gilead, GSK, Healthcare Celltrion, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz and UCB. D. McGonagle: Grants/research support; DM has received research grants/research support from AbbVie, Celgene, Janssen, Merck, and Pfizer. Other; DM has recevied honoraria or consultation fees and has been paid as a speaker for AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer, and UCB Pharma. B. Ink: Shareholder/stock ownership; BI is a shareholder of AbbVie, GlaxoSmithKline and UCB Pharma. D. Assudani: Shareholder/stock ownership; Employee and shareholder of UCB Pharma. V. Taieb: Other; VT is employee of UCB Pharma. L.C. Coates: Consultancies; LCC has worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; LCC has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB Pharma. Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma.

Neutrophil function following treatment of psoriatic arthritis patients with secukinumab: altered cytokine signalling but no impairment of host defence.

Identifying that dysfunction of the IL-23/17 axis underlies PsA has led to the development of effective targeted therapies such as the IL-17A inhibitor secukinumab. As IL-17A stimulates the secretion of neutrophil chemoattractants, such as CXCL8 (IL-8), we examined the effect of secukinumab on neutrophil function in PsA. Nineteen patients with active PsA were treated with secukinumab. Clinical response [PsA Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI)] and peripheral blood neutrophil function (apoptosis, receptor expression, phagocytosis/killing, chemotaxis and RNA expression) were measured at 12 week intervals for 48 weeks and compared with age- and sex-matched healthy controls. At 12 weeks, 12/16 (75%) patients had a PsARC response (100% at 36 weeks) and 10/14 (71%) achieved a 90% PASI response. At baseline, there were no differences in PsA neutrophil reactive oxygen species generation, constitutive or cytokine-delayed apoptosis, chemotaxis or phagocytosis of opsonized Staphylococcus aureus compared with healthy controls. Similarly, there were no differences in these functions from baseline to 12 weeks of therapy. However, surface levels of CD11b/CD18 and CD63 increased and expression of CD16 decreased during therapy. In addition, in a subgroup of early (12 week) responders to secukinumab, RNA sequencing revealed transcriptome changes predicting down-regulation of cytokine signalling and chemotaxis pathways and up-regulation of de novo gene expression pathways, including translation initiation, mRNA catabolism and translation. Complex changes in the properties of circulating neutrophils occur with secukinumab treatment in PsA that may indicate altered responsiveness to changes in both local and systemic levels of pro-inflammatory cytokines. However, host defence processes of neutrophils were unaltered.

OA36 Bimekizumab in patients with psoriatic arthritis: achievement and maintenance of Psoriatic Arthritis Response Criteria responses through 3 years in a phase 2b open-label extension study

Abstract Background/Aims Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL17A, has demonstrated an acceptable safety profile with improvements in joint and skin outcomes to 3 years in patients with active psoriatic arthritis (PsA). Psoriatic Arthritis Response Criteria (PsARC) response data can help relate clinical trial data to UK clinical practice. We report PsARC response rates to 3 years in patients with active PsA from the phase 2b 48-week (wk) dose-ranging study BE ACTIVE (NCT02969525) and its open-label extension (OLE)(NCT03347110). Methods In BE ACTIVE, patients were randomised (1:1:1:1:1) to placebo, BKZ 16mg, BKZ 160mg (with or without 320mg loading dose), or BKZ 320mg, every 4 wks (Q4W). At Wk12, patients assigned to placebo or BKZ 16mg were reassigned (1:1) to dose-blind BKZ 160mg or 320mg Q4W; other patients remained on their original dose. From Wk48 all patients received open-label BKZ 160mg Q4W. We report PsARC to Wk152 and maintenance of response among patients with PsARC response at Wk12, for the full analysis set (FAS). Data are reported as observed and with NRI. Results 206 patients were randomised at baseline in BE ACTIVE and included in the FAS. 181 patients entered the OLE and 161 completed the OLE. 157 patients had calculable PsARC response at Wk152. At Wk12, PsARC response (NRI) was achieved by 125/206, including placebo: 33.3% (14/42), BKZ 16mg: 56.1% (23/41), 160mg: 73.2% (60/82), 320mg: 68.3% (28/41) (Table). At Wk48 and Wk152, 78.2% (161/206) and 68.0% (140/206) patients were PsARC responders, respectively. Of the 125 PsARC responders at Wk12, 88.8% (111/125) also met PsARC at Wk48 and 74.4% (93/125) were PsARC responders at Wk152 (NRI). Over 152 wks, the exposure-adjusted incidence rate per 100 patient-years was 126.4 for all treatment-emergent adverse events (TEAEs), 4.1 for serious TEAEs, 0.7 for serious infections and 4.6 for Candida infections. Conclusion A numerically higher proportion of patients achieved PsARC response in all BKZ-treated groups at Wk12, compared with placebo. The PsARC response rate was sustained through 3 years. Nearly three-quarters of patients who achieved PsARC at Wk12 were also PsARC responders at Wk152. No new safety signals were observed. Disclosure W. Tillett: Consultancies; WT has received consulting fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Honoraria; WT has received honoraria from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Grants/research support; WT has received research grants from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma. I.B. McInnes: Consultancies; IBM has received consulting fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, UCB Pharma. Honoraria; IBM has received honoraria from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, UCB Pharma. Grants/research support; IBM has received research support from Boehringer Ingelheim, BMS, Celgene, Janssen and UCB Pharma. D. McGonagle: Consultancies; DM has received consulting fees from AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Honoraria; DM has received honoraria from AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; DM has been on speaker’s bureau for AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Grants/research support; DM has received grants/research support from AbbVie, Celgene, Janssen, Merck, Pfizer and Novartis. D.R. Jadon: Consultancies; DRJ has received consultancy fees from AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, GSK, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma. Grants/research support; DRJ has received research grants from AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, GSK, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB Pharma. B. Ink: Corporate appointments; BI is an employee of UCB Pharma. Shareholder/stock ownership; BI is a shareholder of GSK and UCB Pharma. D. Assudani: Corporate appointments; DA is an employee of UCB Pharma. Shareholder/stock ownership; DA is a shareholder of UCB Pharma. J. Coarse: Corporate appointments; JC is an employee of UCB Pharma. Shareholder/stock ownership; JC is a shareholder of UCB Pharma. J. Eells: Corporate appointments; JE is an employee of UCB Pharma. Shareholder/stock ownership; JE is a shareholder of UCB Pharma. L.C. Coates: Consultancies; LCC has received consulting fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead and Janssen. Member of speakers’ bureau; LCC has been on speaker’s bureau for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB Pharma. Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma.

Real-World Efficacy and Safety of Apremilast in Belgian Patients with Psoriatic Arthritis: Results from the Prospective Observational APOLO Study.

IntroductionApremilast is approved for the treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on the efficacy and safety of apremilast in clinical practice is limited. We assessed the use of apremilast in patients with PsA in Belgium clinical practice.MethodsThe multicentre, observational, prospective APOLO study enrolled patients with active PsA initiating apremilast in Belgium between April 2017 and December 2018. Primary outcome was PsA Response Criteria (PsARC) after 6 months of apremilast treatment. Secondary outcomes included PsA Impact of Disease 12 (PsAID12) and Health Assessment Questionnaire Disability Index (HAQ-DI). Disease-specific outcomes and patient-reported outcomes (PROs) were analysed for patients who received apremilast within 30 days prior to their study inclusion and completed at least 150 days of treatment (reference set [REF]).ResultsOf 107 patients enrolled in the study, 106 received at least one dose of apremilast and 69 were included in the REF. PsARC response was achieved by 43.5% of patients (30/69) in the REF at month 6; mean global and composite scores including 68-joint count for pain/tenderness (68-TJC) and 66-joint count for swelling (66-SJC) improved, and 27% and 42% of patients with 68-TJC and 66-SJC > 0 at baseline had complete joint count resolution, respectively. Mean global and composite PsAID12 and HAQ-DI scores decreased at 6 months, indicating improved quality of life. Apremilast was well tolerated and the reported adverse events were in line with the known safety profile.ConclusionResults from the APOLO study indicate that treatment with apremilast in Belgian clinical practice improves the signs and symptoms of PsA as well as patient quality of life.Clinicaltrials.gov IdentifierNCT03096990.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-02016-x.

A phase 1 study to assess the safety, pharmacokinetics, and anti-tumor activity of the androgen receptor n-terminal domain inhibitor epi-506 in patients with metastatic castration-resistant prostate cancer

EPI-506 is the first of a new class of drugs targeting the N-terminal domain (NTD) of the androgen receptor (AR), potentially overcoming known resistance mechanisms to androgen receptor pathway inhibitors (ARPIs) among men with metastatic castration resistant prostate cancer (mCRPC). Patients with mCRPC who had progressed on prior ARPI were enrolled in this phase 1 open-label, adaptive 3 + 3 dose escalation study. The primary outcome was safety and tolerability of oral EPI-506. Secondary objectives included determination of the maximal tolerated dose (MTD), pharmacokinetic profile, and antitumor efficacy. 28 mCRPC patients were enrolled into 7 dose cohorts of EPI-506 ranging from 80-3600mg given once daily and 1800mg given twice daily. Six DLTs occurred in 4 patients; Grade 4 elevated amylase; Grade 3 abdominal pain; Grade 3 elevated ALT and Grade 3 elevated AST; Grade 2 nausea and Grade 1 vomiting which resulted in study drug intake of < 75% of the expected dose during the DLT assessment period. The most common drug-related adverse events included diarrhea, nausea and fatigue. Six patients had a PSA decline not meeting PSA response criteria. The study was terminated prior to reaching the MTD due to poor oral bioavailability. This phase 1 trial established the safety of EPI-506 and provides proof of concept for targeting the AR NTD. Next generation compounds with improved bioavailability and potency are in clinical development.

P174 Upadacitinib response rates in patients with psoriatic arthritis enrolled in the SELECT-PsA-1 and SELECT-PsA-2 trials assessed according to modified PsARC

P174 Upadacitinib response rates in patients with psoriatic arthritis enrolled in the SELECT-PsA-1 and SELECT-PsA-2 trials assessed according to modified PsARC

Cost-effectiveness analysis of ixekizumab versus secukinumab in patients with psoriatic arthritis and concomitant moderate-to-severe psoriasis in Spain

ObjectiveTo conduct a cost-effectiveness analysis from the perspective of the Spanish National Health System (NHS) comparing ixekizumab versus secukinumab.DesignA Markov model with a lifetime horizon and monthly cycles was developed...

Systematic literature review of non-topical treatments for early, untreated (systemic therapy naïve) psoriatic disease: a GRAPPA initiative.

BackgroundPsoriatic disease (PsD) is a complex systemic disorder with cutaneous and musculoskeletal manifestations. Current evidence on pharmacological interventions, effective across the spectrum of clinical manifestations of early, systemic treatment-naïve PsD, is limited. This review aims to appraise such evidence.MethodsThis systematic review examined seven patient–intervention–comparator–outcome research questions to address the efficacy of the interventions on the following: across the spectrum of clinical manifestations PsD activity; peripheral arthritis; dactylitis; spondylitis; enthesitis; skin; and nails. Early PsD was defined as a disease duration of ≤2 years, except for studies investigating outcomes restricted to the skin. Eligible references were clinical trials or well-designed prospective studies/series reporting on adult humans, untreated, with cutaneous and/or musculoskeletal features of PsD.ResultsNine references (out of 160 319, publication range 1946–2019) fulfilled the eligibility criteria. No study adopted comprehensive (that is, simultaneous assessment of different PsD manifestations) composite indices as primary outcome measures. Individual studies reported that apremilast and biologics successfully improved outcomes (disease activity index for PsA, minimal disease activity, PsA DAS, psoriasis area and severity index, PsA response criteria) when efficacy analyses were restricted to single manifestations of untreated PsD. Only qualitative synthesis of evidence was possible, owing to the following factors: data heterogeneity (disease classification criteria, outcome measures); unavailable data subsets (focused on early, untreated PsD) at the single study level; and insufficient data on the exposure of participants to previous treatment.ConclusionEffective interventions, albeit limited in scope, were found for early, treatment-naïve PsD. No study provided evidence about the management of co-occurring cutaneous and musculoskeletal manifestations in early, treatment-naïve PsD. This review highlights an unmet need in research on early PsD.

OP0226 NETAKIMAB DECREASES DISEASE ACTIVITY IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM A RANDOMIZED DOUBLE-BLIND PHASE 3 CLINICAL TRIAL (PATERA)

Background:Netakimab (NTK) is a humanized anti-interleukin 17A antibody approved for the treatment of moderate-to-severe plaque psoriasis.Objectives:To determine the efficacy and safety of NTK in patients (pts) with active psoriatic arthritis (PsA), based on 24-week (Wk) data from an ongoing phase 3 study (NCT03598751, PATERA).Methods:194 eligible adult pts with PsA (CASPAR, 2006) with inadequate response to csDMARD or one TNFi, were randomized (1:1) to receive NTK 120 mg or placebo (PBO) subcutaneously at Wk 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. 84 pts from PBO arm who did not meet ACR20 (20% improvement of the American College of Rheumatology criteria) by Wk 16 were switched to NTK 120 mg. The primary endpoint was AСR20 at Wk 24. DAPSA (Disease Activity Index for Psoriatic Arthritis), the proportion of pts achieved ACR50/70, minimal disease activity (MDA) (≥5/7 MDA criteria) and Psoriatic arthritis response criteria (PsARC) were also analyzed.Results:Baseline demographics and disease characteristics were similar across treatment arms (Table 1). 80 (82.47%) pts in NTK arm and 9 (9.28%) in the PBO arm achieved ACR20 at Wk 24 (р&lt;0.0001). A significantly greater percentage of NTK-treated pts had ACR50/70, PsARC response, MDA at Wk 24 (Figure 1). By Wk 24 DAPSA significantly improved for NTK vs PBO. DAPSA remission was achieved by 36.08% and 13.40% in NTK and PBO arms, respectively (p=0.003). NTK was well tolerated. The most frequent AEs (≥3%) were lymphopenia, neutropenia, hypercholesterolemia, ALT increased, upper respiratory tract infection, systolic blood pressure increased, hyperglycemia, hyperbilirubinemia. Most AEs were mild to moderate. Severe treatment-related AEs were observed in 1.03% vs 2.06% for NTK and PBO, respectively. No treatment-related SAEs were reported. No anti-drug antibodies were detected.Table 1.Baseline demographics and disease severity characteristicsArmNTK (N=97)PBO (N=97)Age (years) *44.0 (11.66)43.1 (11.88)Male, n (%)52 (53.61)50 (51.55)PsA duration, mo*63.1 (73.12)68.2 (77.49)DAS28-CRP*4.62 (0.97)4.41 (1.11)DAPSA*32.19 (12.23)33.54 (15.98)TJC (66/68) *12.9 (9.97)12.0 (9.88)SJC (66/68) *7.0 (4.93)7.2 (7.18)MTX at baseline83 (85.6)83 (85.6)Previous PsA therapySulfasalazine, n (%)9 (9.28)11 (11.34)Leflunomide, n (%)4 (4.12)8 (8.25)Anti-TNFα, n (%)22 (22.68)17 (17.53)* mean (standard deviation); Mo=months, PsA=psoriatic arthritis, SJC=swollen joint count, TJC=tender joint count, DAS28=Disease Activity Score, MTX=methotrexate, CRP=C-reactive protein, DAPSA=Disease activity index for psoriatic arthritis, TNF=tumor necrosis factorFigure 1.Treatment response at Wk 24Conclusion:NTK is a well-tolerated monoclonal antibody, that provided sustained improvements in signs and symptoms of active PsA through 24 Wks of therapy.Table 2.Safety dataArmNTK (N=97)PBO (N=97)p-valueTreatment-related AEs12 (12.37)7 (7.22)0.2271Treatment-related SAEs0 (0)0 (0)1.002Treatment-related AEs (grade 3-4)1 (1.03)2 (2.06)1.002Local reactions0 (0)0 (0)-Grade 3-4 treatment-related AEsblood pressure increased1 (1.03)0(0)1.002lymphopenia0 (0)2 (2.06)0.4972n (%) are presented,1Pearson’s χ2test,2Fisher’s exact test; N=number of patients, AE=adverse event, SAE=serious adverse event, ALT=Alanine transaminaseAcknowledgments:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Tatiana Korotaeva Consultant of: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, V Mazurov: None declared, Aleksey Samtsov Grant/research support from: JSC BIOCAD, Novartis, Eli Lilly, Johnson&amp;Johnson, Celgene, Glenmark, Galderma, Sanofi, Vladislav Khayrutdinov Grant/research support from: Akrikhin, Alkoy, Belupo, JSC BIOCAD, Bosnaliejk, Verteks, Glenmark, Elfa, Leo Pharma, MSD, Novartis, Pfizer, Sun Pharma, Sanofi, Celgene, Pharmtec, AbbVie, Eli Lilly, Jadran, Janssen, Andrey Bakulev Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&amp;Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&amp;Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&amp;Johnson, Muza Kokhan Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&amp;Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&amp;Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&amp;Johnson, Alena Kundzer: None declared, Nikolaj Soroka Grant/research support from: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Anna Eremeeva Employee of: JSC BIOCAD

Cost-Effectiveness Analysis of Sequential Biologic Therapy with Ixekizumab Versus Secukinumab in the Treatment of Active Psoriatic Arthritis with Concomitant Moderate-to-Severe Psoriasis in the UK

BackgroundInterleukin-17A (IL-17A) antagonists are a recent innovation for treating psoriatic arthritis (PsA). There are currently no cost-effectiveness analyses (CEAs) comparing the IL-17A antagonists ixekizumab and secukinumab in PsA from a UK perspective.ObjectiveWe conducted a CEA from the UK National Health Service perspective to compare ixekizumab versus secukinumab in patients with PsA and concomitant moderate-to-severe plaque psoriasis.MethodsA Markov model was developed based on the widely accepted York model. In biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, ixekizumab → ustekinumab → best supportive care (BSC) was compared with secukinumab → ustekinumab → BSC. For bDMARD-experienced patients, ixekizumab → BSC was compared with secukinumab → BSC. At the end of the bDMARD trial period, Psoriatic Arthritis Response Criteria (PsARC) responders continued to receive the bDMARD in the continuous treatment period. PsARC nonresponders and patients who ceased continuous treatment transitioned to the trial period of the next treatment.ResultsIxekizumab was less costly and provided more quality-adjusted life-years (QALYs) than secukinumab in bDMARD-naïve and -experienced patients based on list prices, although cost savings and QALY gains were small to modest. In bDMARD-naïve patients, total costs were £155,455 compared with £155,530 for secukinumab (year 2017 values). Total QALYs were 8.127 versus 7.989. In bDMARD-experienced patients, the corresponding values were £140,051 versus £140,264 for total costs and 3.996 versus 3.875 for total QALYs.ConclusionIxekizumab provided more QALYs at a marginally lower cost than secukinumab, and the results were most sensitive to changes in drug costs. Other factors, such as patient preferences for the number of injections and confidential price discounts, may be important considerations in clinical decision-making.Electronic supplementary materialThe online version of this article (10.1007/s41669-020-00202-1) contains supplementary material, which is available to authorized users.

Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis

BackgroundBiologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly compare their clinical efficacy. In such situations, network meta-analysis...

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.

Real-World Experience of Apremilast in Treating Psoriatic Arthritis Patients with Comorbidities

This observational study aimed to evaluate the efficacy and real-world experience of apremilast (APR) in treating psoriatic arthritis (PsA) patients with co-existing conditions presenting to clinic. Data from 28 patients treated with APR for PsA were collected between January 2016 and January 2019. Outcome measures disease activity score 44-C-reactive protein (DAS44-CRP), 0–68 for tender and 0–66 for swollen joint count, were collected at Weeks 0, 16, and 52. Response was classified using the Psoriatic Arthritis Response Criteria (PsARC). Adverse events or worsening of pre-existing conditions were recorded. Results included outcomes at Weeks 16 and 52 which showed a percentage reduction in mean DAS44-CRP at Weeks 16 and 52 by -1.4 and -1.9, respectively. There was percentage reduction at Weeks 16 and 52 of tender (-55.5%, -75.4%) and swollen (-45.8%, -61.5%) joint counts from baseline. It was also found that 19/28 (68.0%) patients were responders by PsARC criteria up to Week 52. Responders had shorter disease duration (mean: 4.9 years, standard deviation: 1.9) and lower previous exposure to biologic disease-modifying antirheumatic drugs (bDMARD); 16/19 subjects (84.0%) had no previous bDMARD. There were no serious adverse events during the study and no worsening of co-existing conditions during treatment. In this real-world observational study, APR was shown to be effective in PsA patients with multiple co-existing conditions. APR was more effective in PsA patients with shorter disease duration and in bDMARD naïve patients. APR provides another effective treatment option for PsA patients with multiple co-existing conditions.

Efficacy and safety of leflunomide in psoriatic arthritis treatment: A single-arm meta-analysis.

To systematically assess the clinical efficacy and safety of leflunomide for treating psoriatic arthritis (PsA). PubMed, Embase, and Cochrane Library databases were searched until 1 January, 2018, to include relevant studies in this single-arm meta-analysis. Psoriasis improvement was evaluated using Psoriasis Area and Severity Index (PASI) scores. The primary outcome in patients was assessed using the Psoriatic Arthritis Response Criteria (PsARC). Other effectiveness evaluations included those of adverse events, quality of life including functional status (Health Assessment Questionnaire [HAQ] total score), and a quality-of-life instrument for dermatologic diseases (Dermatology Life Quality Index [DLQI] total score). A total of 6 studies were included. After leflunomide treatment, 48% of the patients experienced a reduction of ≥50% based on PASI scores (95% confidence interval [CI]: 0.22-0.73). PASI 75 improvement was observed among 25% of the patients (95% CI: 0.11-0.38). The primary effectiveness analysis revealed that 15% of the patients (95% CI: 0.07-0.26) discontinued leflunomide treatment. Further, 77% of the patients (95% CI: 0.59-0.92) achieved a PsARC response. Adverse events occurred in 38% of the patients (95% CI: 0.04-0.71). The mean±SD percentage PASI improvement was -4.88 (95% CI: -8.92, -0.85). Moreover, DLQI and HAQ were -2.02 (95% CI: -3.01, -1.03) and -0.19 (95% CI: -0.29, -0.09), respectively. Leflunomide is an effective and well-tolerated treatment for PsA, and would be a safe and convenient option.

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.