scholarly journals LB0001 EFFICACY AND SAFETY OF UPADACITINIB VERSUS PLACEBO AND ADALIMUMAB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND INADEQUATE RESPONSE TO NON-BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (SELECT-PsA-1): A DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE 3 TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 16.2-17
Author(s):  
I. Mcinnes ◽  
J. Anderson ◽  
M. Magrey ◽  
J. F. Merola ◽  
Y. Liu ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Study Drug ◽  
Musculoskeletal Symptoms ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Research Support ◽  
Self Assessment ◽  
Double Blind ◽  
Biologic Dmard ◽  
Secondary Endpoints

Background:Upadacitinib (UPA) is an oral, reversible, JAK inhibitor approved for treatment of rheumatoid arthritis (RA) and currently under evaluation for treatment of psoriatic arthritis (PsA).Objectives:To assess the efficacy and safety of UPA vs placebo (PBO) and adalimumab (ADA) in patients (pts) with PsA and prior IR or intolerance to ≥1 non-biologic DMARD (non-bDMARD).Methods:Pts with active PsA (≥3 swollen and ≥3 tender joints), active or historical psoriasis, and on ≤2 non-bDMARDs were randomized 1:1:1:1 to once daily UPA 15 mg (UPA15), UPA 30 mg (UPA30), ADA 40 mg every other week, or PBO. The primary endpoint was the proportion of pts achieving ACR20 for UPA vs PBO at Wk 12. Multiplicity controlled secondary endpoints for each dose of UPA vs PBO included change in HAQ-DI, FACIT-F, and SF-36 PCS (Wk 12); static Investigator Global Assessment of Psoriasis of 0 or 1, PASI75, and change in Self-Assessment of Psoriasis Symptoms (Wk 16); change in modified Sharp/van der Heijde Score (mTSS), proportion of pts achieving MDA, and resolution of enthesitis (LEI=0) and dactylitis (LDI=0) (Wk 24). For each dose of UPA, the multiplicity-controlled analysis also included non-inferiority and superiority vs ADA for ACR20 and superiority for HAQ-DI and pt’s assessment of pain NRS (Wk 12). ACR50/70 at Wk 12 and ACR20 at Wk 2 were additional secondary endpoints. Treatment-emergent adverse events (TEAEs) through 24 wks are reported for pts who received ≥1 dose of study drug.Results:1705 pts were randomized; 1704 received study drug (53.2% female, mean age 50.8 yrs, mean duration of PsA diagnosis 6.1 yrs). 82% were on ≥1 concomitant non-bDMARD, of whom 84% received MTX +/- another non-bDMARD.At Wk 12, ACR20 rates were 70.6% with UPA15 and 78.5% with UPA30 vs 36.2% with PBO (p < .001 for UPA15/30 vs PBO) and 65.0% with ADA (non-inferiority, p < .001 for UPA15/30 vs ADA; superiority, p < .001 for UPA30 vs ADA). A greater proportion of pts achieved ACR50/70 with UPA15/30 vs PBO and UPA30 vs ADA. Improvements were observed with UPA15/30 vs PBO for all multiplicity controlled secondary endpoints and for UPA 15/30 vs ADA for HAQ-DI and UPA 30 vs ADA for improvement in pain (Figure 1A-1B). At Wk 24, change in mTSS was 0.25 for PBO, -0.04 for UPA15, 0.03 for UPA30, and 0.01 for ADA (p < 0.001 for UPA15/30 vs PBO). The rates of TEAEs and serious AEs, including serious infections, were similar in the PBO, UPA15, and ADA arms and higher with UPA30 (Figure 2). The rate of herpes zoster was similar for PBO and UPA15/30. No MACE was reported with UPA. One malignancy occurred in each of the PBO and UPA15 arms, and 3 malignancies were reported in each of the UPA30 and ADA arms. VTE were reported in 1 pt on PBO, 1 pt on UPA30, and 2 pts on ADA. One death occurred in the PBO arm.Conclusion:In this non-bDMARD-IR PsA population, treatment with UPA15/30 demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, and fatigue and inhibited radiographic progression; improvements were observed by Wk 2. At Wk 12, UPA15/30 were non-inferior to ADA for ACR20, with superiority demonstrated for UPA30. Greater percentages of UPA vs PBO pts achieved stringent measures of disease control (MDA, ACR50/70, sIGA 0/1). No new safety signals were identified compared with the safety profile observed in RA.Disclosure of Interests:Iain McInnes: None declared, Jaclyn Anderson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Marina Magrey Grant/research support from: Amgen, AbbVie, and UCB Pharma, Consultant of: Novartis, Eli Lilly, Pfizer, and Janssen, Joseph F. Merola Consultant of: Merck, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma, Yi Liu: None declared, Mitsumasa Kishimoto Consultant of: bbVie, Eli Lilly, Celgene, Pfizer, Gilead, Janssen, and UCB Pharma, Speakers bureau: AbbVie, Eisai, Celgene, Pfizer, Novartis, Eli Lilly, Tanabe-Mitsubishi, Ayumi, Janssen, Astellas, and UCB Pharma, Sławomir Jeka Speakers bureau: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Cesar Francisco Pacheco Tena: None declared, xin wang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Liang Chen Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Patrick Zueger Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, UCB, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai

scholarly journals P173 Efficacy and safety of upadacitinib versus placebo and adalimumab in patients with active PsA and inadequate response to non-biologic DMARDs (SELECT-PSA-1): a double-blind, randomised controlled phase III trial

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Iain McInnes ◽  
Jaclyn Anderson ◽  
Marina Magrey ◽  
Joseph F Merola ◽  
Yi Liu ◽  
...  
Keyword(s):  
Study Drug ◽  
Control Measures ◽  
Phase Iii ◽  
Musculoskeletal Symptoms ◽  
Stock Ownership ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Research Support ◽  
Double Blind ◽  
Secondary Endpoints

Abstract Background/Aims  Upadacitinib (UPA) is a JAK inhibitor under evaluation for PsA treatment. We aimed to assess efficacy and safety of UPA vs placebo (PBO) and adalimumab (ADA) in patients with prior inadequate response (IR) or intolerance to ≥ 1 non-biologic DMARD. This research was previously presented at EULAR; published in Annals of Rheumatic Diseases. Methods  Patients with active PsA (≥3 swollen, ≥3 tender joints), active/historical psoriasis, ≤2 non-bDMARDs were randomized 1:1:1:1 to once-daily UPA 15mg (UPA15), UPA 30mg (UPA30), ADA 40mg every other week, or PBO. Primary endpoint: proportion of patients achieving ACR20 for UPA vs PBO at Wk12. Secondary endpoints: change in HAQ-DI, FACIT-F, SF-36-PCS (Wk12), sIGA of Psoriasis 0/1, PASI75, change in Self-Assessment of Psoriasis Symptoms (Wk16), change in modified Sharp/van der Heijde Score (mTSS), proportion patients achieving MDA, resolution of enthesitis (LEI=0) and dactylitis (LDI=0) (Wk24), non-inferiority and superiority vs ADA for ACR20, superiority for HAQ-DI, patient assessment of pain NRS (Wk12). Additional secondary endpoints: ACR50/70 at Wk12 and ACR20 at Wk2. Treatment-emergent adverse events (TEAEs) through Wk24 reported for patients receiving ≥1 dose of study drug. Results  1,705 patients were randomised; 1,704 received study drug (mean age 50.8 yrs, mean duration of PsA diagnosis 6.1 yrs). 82% on ≥ 1 concomitant non-bDMARD. At Wk12, ACR20 rates were 70.6% with UPA15 and 78.5% with UPA30 vs 36.2% with PBO (p &lt; 0.001 for UPA15/30 vs PBO) and 65.0% with ADA (non-inferiority, p &lt; 0.001 for UPA15/30 vs ADA; superiority, p &lt; 0.001 for UPA30 vs ADA). More patients achieved ACR50/70 with UPA15/30 vs PBO and UPA30 vs ADA. Improvements were observed with UPA15/30 vs PBO for all secondary endpoints and for UPA 15/30 vs ADA for HAQ-DI and UPA30 vs ADA for improvement in pain. At Wk24, change in mTSS was 0.25 for PBO, -0.04 for UPA15, 0.03 for UPA30, and 0.01 for ADA (p &lt; 0.001 for UPA15/30 vs PBO). Rates of TEAEs and serious AEs, including serious infections, were similar in PBO, UPA15, and ADA arms and higher with UPA30. Herpes zoster rates were similar for PBO and UPA15/30. No MACE was reported with UPA. One malignancy occurred in both the PBO and UPA15 arms; 3 malignancies were reported in both UPA30 and ADA arms. VTE were reported in 1 PBO patient, 1 UPA30 patient and 2 ADA patients. One death occurred in the PBO arm. Conclusion  In this non-bDMARD-IR PsA population UPA15/30 demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, fatigue and inhibited radiographic progression; improvements observed by Wk2. At Wk12, UPA15/30 were non-inferior to ADA for ACR20, with superiority demonstrated for UPA30. Greater percentages of UPA vs PBO patients achieved stringent disease control measures (MDA, ACR50/70, sIGA 0/1). No new safety signals were identified compared to the safety profile observed in RA. Disclosure  I. McInnes: Other; I.McI has received research grants and honoraria from Abbvie, BMS, Celgene, Novartis Lilly, Janssen, Pfizer, UCB. J. Anderson: Shareholder/stock ownership; J.A. may be a stock/ shareholder of AbbVie Inc. M. Magrey: Consultancies; M.M. has received consulting fees from Novartis, Eli Lilly, Pfizer, and Janssen. Grants/research support; M.M. has received grants/ research support from Amgen, AbbVie, and UCB Pharma. J.F. Merola: Consultancies; J.F.M. is a consultant for Merck, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma. Y. Liu: None. M. Kishimoto: Consultancies; M.K. has received consulting fees from AbbVie, Eli Lilly, Celgene, Pfizer, Gilead, Janssen, and UCB Pharma. Honoraria; M.K. has received honoraria/ speakers fees from AbbVie, Eisai, Celgene, Pfizer, Novartis, Eli Lilly, Tanabe-Mitsubishi, Ayumi, Janssen, Astellas, and UCB Pharma. S. Jeka: None. C. Pacheco-Tena: None. X. Wang: Shareholder/stock ownership; X.W. may be a shareholder of AbbVie Inc. L. Chen: Shareholder/stock ownership; L.C. may be a stock/shareholder of AbbVie Inc. P. Zueger: Shareholder/stock ownership; P.Z. may be a stock/shareholder of AbbVie Inc. A. Pangan: Shareholder/stock ownership; A.P. may be a stock/shareholder of AbbVie Inc. F. Behrens: Honoraria; F.B. has received honoraria and speakers fees from Pfizer, AbbVie, Sanofi, Lilly, Novartis, UCB, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai. Grants/research support; F.B. has received grants/ research support from Pfizer, Janssen, Chugai, Celgene and Roche.

scholarly journals Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial

2021 ◽  
pp. annrheumdis-2021-221048
Author(s):  
Andrew Östör ◽  
Filip Van den Bosch ◽  
Kim Papp ◽  
Cecilia Asnal ◽  
Ricardo Blanco ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Primary Endpoint ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Patient Reported ◽  
Secondary Endpoints

ObjectivesRisankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here.MethodsAdults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes.ResultsA total of 444 patients (median age 53 years, range 23–84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, p<0.001) and all secondary endpoints (p<0.05) compared with placebo. Serious adverse events were reported for 4.0% and 5.5% of risankizumab-treated and placebo-treated patients, respectively; serious infections were reported for 0.9% and 2.3%, respectively.ConclusionTreatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR.Trial registration numberNCT03671148.

scholarly journals OP0053 SECUKINUMAB IMPROVES CLINICAL AND IMAGING OUTCOMES IN PATIENTS WITH PSORIATIC ARTHRITIS AND AXIAL MANIFESTATIONS WITH INADEQUATE RESPONSE TO NSAIDS: WEEK 52 RESULTS FROM THE MAXIMISE TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 35-36 ◽  
Author(s):  
X. Baraliakos ◽  
L. Gossec ◽  
E. Pournara ◽  
S. Jeka ◽  
R. Blanco ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Controlled Trial ◽  
Spinal Pain ◽  
Inadequate Response ◽  
Imaging Data ◽  
Sacroiliac Joints ◽  
Research Support ◽  
Double Blind ◽  
Randomised Controlled ◽  
Mri Score

Background:Although axial disease may affect up to 70% of patients (pts) with Psoriatic Arthritis (PsA), evidence on the efficacy of biologics in the treatment of axial manifestations in such pts is limited,1particularly as validated classification criteria for this subtype of PsA are not yet available. MAXIMISE (NCT02721966) is the first randomised controlled trial evaluating the efficacy of a biologic in the management of the axial manifestations of PsA and showed that secukinumab (SEC) 300 and 150 mg provided rapid and significant improvement in ASAS20 responses in these pts through week (Wk) 12.2Objectives:To present 52 wks efficacy results and imaging data from the MAXIMISE trial.Methods:This phase 3b, double-blind, placebo (PBO)-controlled, multicentre 52-wk trial included 498 pts (aged ≥18 years) with a diagnosis of PsA and classified by CASPAR criteria, spinal pain VAS score ≥ 40/100 and BASDAI score ≥ 4 despite use of at least two NSAIDs. Pts were randomised to SEC 300 mg (N=167) or SEC 150 mg (N=165) or PBO (N=166) wkly for 4 wks and every 4 wks thereafter. At Wk 12, PBO pts were re-randomised to SEC 300/150 mg. The primary endpoint was ASAS20 response with SEC 300 mg at Wk 12. The key secondary endpoint was ASAS20 response with SEC 150 mg at Wk 12. Wk 52 data are presented as observed. Bone marrow oedema of the entire spine and sacroiliac joints were assessed centrally with Berlin MRI scores at Baseline, Wk 12 and Wk 52.Results:Primary and key secondary endpoints were met; ASAS20 responses were sustained and increased further through Wk 52. 75%/79.7% of the PBO pts re-randomised at Wk 12 to SEC 300/150 mg achieved ASAS20 response at Wk 52 (Figure 1). ASAS40 responses at Wk 52 were 69.1% [SEC 300 mg], 64.5% [SEC 150 mg], 62.5% [PBO-SEC 300 mg], and 54.1% [PBO-SEC 150 mg]. At baseline, 59.5% [SEC 300 mg], 53.5% [SEC 150 mg] and 64.2% [PBO] of the pts had positive MRIs for the sacroiliac joints and/or the spine with Berlin MRI score ≥1. The reductions of Berlin MRI score for entire spine and sacroiliac joints were statistically significant for pts treated with SEC 300/150 mg vs. placebo (Figure 2a and b). There were no new or unexpected safety findings.Figure 1.ASAS20 Response over 52 Wks*Figure 2.Total Berlin MRI score for the Entire Spine and Sacroiliac Joints at Wk 12Conclusion:Secukinumab improved all evaluated ASAS responses through Wk 52 in PsA pts with axial manifestations and inadequate responses to NSAIDs and led to significant reduction of inflammatory MRI lesions in the spine and the Sacroiliac Joints. The safety profile of secukinumab through Wk 52 was consistent with previous reports.3-4References:[1]McInnes IB, et al.Lancet.2015;386(9999):1137–46.[2]Baraliakos X, et al.Arthritis Rheumatol. 2019;71 (suppl 10).[3]Langley RG, et al.N Engl J Med.2014;371:326–38.[4]Sieper J, et al.Ann Rheum Dis.2016;0:1–8.Acknowledgments:The study was sponsored by Novartis Pharma AG, Basel, Switzerland.Disclosure of Interests:Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Effie Pournara Shareholder of: Novartis, Employee of: Novartis, Sławomir Jeka Grant/research support from: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Salvatore D’Angelo Consultant of: AbbVie, Biogen, BMS, Celgene, Eli Lilly, MSD, Novartis, and UCB, Speakers bureau: AbbVie, BMS, Celgene, Eli Lilly, Novartis, Pfizer, and Sanofi, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Barbara Schulz Employee of: Novartis, Michael Rissler Shareholder of: Novartis, Employee of: Novartis, Kriti Nagar Employee of: Novartis, Chiara Perella Shareholder of: Novartis, Employee of: Novartis, Laura C Coates: None declared

scholarly journals POS0198 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 314.2-315
Author(s):  
P. J. Mease ◽  
A. Deodhar ◽  
D. Van der Heijde ◽  
F. Behrens ◽  
A. Kivitz ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Tyrosine Kinase ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Research Support ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Phase 2 Trial ◽  
Tyrosine Kinase 2 ◽  
Sf 36

Background:Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signaling by key cytokines involved in psoriatic arthritis (PsA) and plaque psoriasis (PsO) pathogenesis. Deucravacitinib is a novel oral agent that selectively inhibits TYK2 via an allosteric mechanism by binding to the nonconserved regulatory domain of the kinase. A previous Phase 2 trial in PsO had demonstrated that deucravacitinib was efficacious and well tolerated, with no laboratory abnormalities observed.Objectives:To evaluate the efficacy and safety of deucravacitinib in active PsA.Methods:This is an ongoing, 1-year, randomized, double-blind, placebo (PBO)-controlled (initial 16 weeks), multiregional, Phase 2 trial (NCT03881059). Eligible patients had a PsA diagnosis for ≥6 months, met CASPAR criteria, and had active disease with ≥3 tender and ≥3 swollen joints, C-reactive protein ≥3 mg/L (ULN, 5 mg/L), and ≥1 psoriatic lesion (≥2 cm). Patients had failed or were intolerant to ≥1 nonsteroidal anti-inflammatory drug, corticosteroid, conventional synthetic disease-modifying antirheumatic drug (csDMARD), and/or 1 TNF inhibitor (TNFi; ≤30%). Patients were randomized 1:1:1 to deucravacitinib 6 mg once daily (QD) or 12 mg QD, or PBO. The primary endpoint was achievement of ACR 20 response at Week 16. Additional endpoints included the proportion of patients achieving ACR 50/70 response, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (≥0.35 improvement from baseline), enthesitis resolution (Leeds Index score of 0), minimal disease activity, change from baseline in SF-36 physical component score (SF-36 PCS) and mental component score (SF-36 MCS), Psoriasis Area and Severity Index (PASI) 75 response, adverse events (AEs), and laboratory parameters.Results:Of 203 patients randomized, 180 (89%) completed 16 weeks of treatment (deucravacitinib 6 mg QD, 63/70 [90%]; deucravacitinib 12 mg QD, 59/67 [88%]; PBO, 58/66 [88%]). Demographic and baseline disease characteristics were similar across groups. Mean age was 49.8 years, 51% of patients were female, median PsA duration was 4.5 years, 66% of patients used csDMARDs at baseline and throughout the study, and 15% had used a TNFi. This study met its primary endpoint, with deucravacitinib 6 mg and 12 mg QD demonstrating significantly higher ACR 20 responses versus PBO at Week 16 (Figure 1). Additional endpoints were also met with deucravacitinib versus PBO (Figure 1). Adjusted mean changes from baseline in SF-36 PCS and SF-36 MCS at Week 16, respectively, were significantly higher in the deucravacitinib 6 mg QD group (5.6 vs 2.3, P=0.0062; 3.6 vs 0.7, P=0.0211) and 12 mg QD group (5.8 vs 2.3, P=0.0042; 3.5 vs 0.7, P=0.0263) compared with PBO. PASI 75 responses were also significantly higher in the deucravacitinib groups (P≤0.0136 vs PBO). The most common AEs in the deucravacitinib 6 mg/12 mg/PBO groups, respectively, during the 16-week treatment period were nasopharyngitis (5.7%/17.9%/7.6%), sinusitis (0%/7.5%/0%), headache (7.1%/1.5%/4.5%), and rash (4.3%/6.0%/0%). No serious AEs, herpes zoster infections, opportunistic infections, or thrombotic events were reported in deucravacitinib-treated patients during this period. Additionally, no significant changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, and hemoglobin) or serum lipids were observed with deucravacitinib treatment.Conclusion:Deucravacitinib was efficacious versus PBO over 16 weeks in patients with active PsA. Treatment was generally well tolerated and the safety and laboratory parameter profile of deucravacitinib was consistent with that observed in an earlier Phase 2 PsO trial.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Atul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Frank Behrens Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, Bristol Myers Squibb, UCB Pharma, Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Roche, Alan Kivitz Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis, Paid Consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc., Speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie, Jonghyeon Kim Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Shalabh Singhal Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

scholarly journals P210 Efficacy and safety of filgotinib for patients with RA with inadequate response to methotrexate: FINCH1 primary outcome results

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
David Walker ◽  
Bernard G Combe ◽  
Alan J Kivitiz ◽  
Yoshiya Tanaka ◽  
Désirée van der Heijde ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Study Drug ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Mixed Effect ◽  
Patient Reported

Abstract Background Filgotinib (FIL) is an oral, potent, selective Janus kinase 1 inhibitor that has shown good efficacy and was well tolerated for treatment of rheumatoid arthritis (RA). The objective of this study was to evaluate efficacy and safety of FIL treatment in patients with RA who have had an inadequate response to methotrexate (MTX). Methods This Phase 3, double-blind, active- and placebo (PBO)-controlled study randomised patients with active RA (3:3:2:3) to FIL 200mg, FIL 100mg, adalimumab [ADA] 40mg every 2 weeks, or PBO daily for up to 52 weeks; results through week 24 are presented. Patients also received background MTX. Primary efficacy endpoint was proportion of patients achieving ACR20 at week 12; additional clinical assessments included ACR50 and ACR70 and DAS28-CRP score ≤3.2 and &lt;2.6, and patient-reported outcomes including HAQ-DI. Safety endpoints included adverse event types and rates. Logistic regression was used for superiority test of FIL vs PBO for ACR response and other binary endpoints, while mixed-effect model for repeated measures (MMRM) were used for continuous endpoints. Non-inferiority test of FIL to ADA (preserving &gt;50% of ADA response) was performed for DAS28-CRP ≤3.2 and &lt;2.6. Results Of 1,759 patients randomised, 1,755 received study drug: 475 FIL 200mg; 480 FIL 100mg; 325 ADA; and 475 PBO, of which 89.5%, 90.4%, 88.9%, and 81.3%, respectively, completed 24 weeks of study drug. 81.8% were female, mean (standard deviation [SD]) duration of RA was 7.8 (7.6) years, and mean (SD) DAS28-CRP was 5.7 (0.9). At week 12, significantly more patients in the FIL 200mg and 100mg arms achieved an ACR20 improvement vs PBO (Table 1). More patients receiving FIL achieved ACR50 and ACR70 improvements, DAS28-CRP scores ≤3.2 and &lt;2.6 and reported improvements in HAQ-DI scores versus PBO (Table 1). Non-inferiority of FIL 200mg to ADA was met based on DAS28-CRP ≤3.2. The FIL safety profile was consistent with prior studies through Week 24. Conclusion FIL 200mg and 100mg led to significant improvement in signs and symptoms of RA, prevented radiographic progression, improved physical function compared to PBO, and was well-tolerated. Efficacy of FIL 200mg was non-inferior to ADA based on DAS28-CRP ≤3.2. Disclosures D. Walker: Other; Received support from Lilly, Pfizer, Novartis and Roche. B.G. Combe: Honoraria; Received honoraria from AbbVie, BMS, Gilead, Janssen, Eli Lilly and Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. A.J. Kivitiz: Consultancies; Consultant to AbbVie, Celgene, Horizon, Jansses, Merck, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron, SUN Pharma Advanced Research, Boehringer Ingelheim, Flexion and Novartis. Shareholder/stock ownership; Shareholder of Novartis. Y. Tanaka: Honoraria; Honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly ans Co., Pfizer, AbbVie, YL Biologics, BMS, Takeda, Misubishi-Tanabe, Novartis, Eisai, Janssen, Teijin. Grants/research support; Grant support from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, BMS, UCB, Daiichi-Sankyo, Eisai, Ono, Astellas, Eli Lilly, Pfizer, Abbvi and YL. D. van der Heijde: Corporate appointments; Director of Imaging Rheumatology bv. Consultancies; Consultant for consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. L. Ye: Corporate appointments; Employee of Gilead Sciences, Inc.. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. C. Tasset: Corporate appointments; Employee of Galapagos NV. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. N. Mozaffarian: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R.B.M. Landewé: Consultancies; Consultant for AbbVie, AstraZeneca, BMS, Galapagos, Pfizer, Eli Lilly, Novartis, and UCB.. S. Bae: None. E.C. Keystone: Consultancies; Consultant for AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer,, PuraPharm, Sandoz, Sanofi-Aventis, Sanofi-Genzyme, Samsumg Bioepsis, and UCB. P. Nash: Consultancies; Consultant for AbbVie, BMS, Jansses, Pfizer, Roche, Lilly, Sanofi, MSD, Novartis, Celgene and Gilead.

scholarly journals Efficacy and safety of netakimab in patients with psoriatic arthritis: results of the phase III PATERA clinical study

2020 ◽  
Vol 58 (5) ◽  
pp. 480-488
Author(s):  
T. V. Korotaeva ◽  
V. I. Mazurov ◽  
A. M. Lila ◽  
I. Z. Gaydukova ◽  
A. L. Bakulev ◽  
...  
Keyword(s):  
Placebo Group ◽  
Psoriatic Arthritis ◽  
Safety Profile ◽  
Phase Iii ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
American College Of Rheumatology ◽  
Blinded Manner

Netakimab (NTK) is a humanized anti-interleukin-17А (IL-17A) monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Here, we present the results of the 24-weeks double blind period of the PATERA study.Objective. The objective of the study was to evaluate the efficacy and safety of NTK compared to placebo in patients with psoriatic arthritis (PsA).Patients and methods. 194 patients with active PsA with an inadequate response to previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs, were randomized in a 1:1 ratio to receive subcutaneous 120 mg NTK or placebo at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 ACR20 (20% improvement in the American College of Rheumatology response criteria) non-responders in placebo group were reassigned to NTK in a blinded manner. The primary endpoint was the proportion of patients achieved ACR20 response at week 24.Results. 82,5% of patients in the NTK group and 9.3% of patients in the placebo group achieved ACR20 at week 24 with the 95% CI [0,63; 0,84] (p < 0,0001). Skin manifestations and axial disease significantly improved with NTK. The safety profile of NTK was comparable to placebo. The most frequent treatment-related AEs were expected and common for all other IL-17 inhibitors: increased alanine aminotransferase (ALT), infections, lymphopenia.Conclusion. NTK in the dose of 120 mg has superior efficacy over placebo in patients with active psoriatic arthritis. The safety profile is consistent with other IL-17 inhibitors.

SAT0151 EFFICACY AND SAFETY OF UPADACITINIB VERSUS ABATACEPT IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE OR INTOLERANCE TO BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (SELECT-CHOICE): A DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE 3 TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1015-1016
Author(s):  
A. Rubbert-Roth ◽  
J. Enejosa ◽  
A. Pangan ◽  
R. Xavier ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Study Drug ◽  
Signs And Symptoms ◽  
Drug Discontinuation ◽  
Inadequate Response ◽  
Research Support ◽  
Phase 3 ◽  
Double Blind ◽  
Biologic Dmards

Background:Upadacitinib (UPA) is an oral, reversible, selective JAK 1 inhibitor approved for the treatment of moderate to severe rheumatoid arthritis (RA). The efficacy/safety of UPA has been demonstrated in phase 3 studies, including superiority to adalimumab in patients (pts) with prior inadequate response (IR) to methotrexate.1-4Objectives:To assess the efficacy/safety of UPA vs abatacept (ABA) in pts with prior IR or intolerance to biologic DMARDs (bDMARDs).Methods:Pts were randomized to once daily UPA 15 mg or intravenous ABA (at Day 1, Weeks [Wks] 2, 4, 8, 12, 16 and 20 [< 60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1,000 mg]), with all pts continuing background stable csDMARDs. The study was double-blind for 24 wks. Starting at Wk 12, pts who did not achieve ≥20% improvement from baseline (BL) in both tender and swollen joint counts at two consecutive visits, had background medication(s) adjusted or initiated. The primary endpoint was change from BL in DAS28(CRP) at Wk 12 (non-inferiority). The non-inferiority of UPA vs ABA was tested using the 95% CI of treatment difference against a non-inferiority margin of 0.6. The two key secondary endpoints at Wk 12 were change from BL in DAS28(CRP) and the proportion of pts achieving clinical remission (CR) based on DAS28(CRP), defined as DAS28(CRP) <2.6. Both endpoints were to demonstrate the superiority of UPA vs. ABA. Treatment-emergent adverse events (TEAEs) are reported up to Wk 24 for all pts who received at least one dose of study drug.Results:Of 612 pts treated; 67% of pts had received 1 prior bDMARD, 22% received 2 prior bDMARDs, and 10% received ≥ 3 prior bDMARDs. 549 (90%) completed 24 wks of treatment. Common reasons for study drug discontinuation were AEs (UPA, 3.6%; ABA, 2.6%) and withdrawal of consent (UPA, 1.7%; ABA, 2.6%).Non-inferiority and superiority were met for UPA vs ABA at Wk 12 for change from BL in DAS28(CRP) (-2.52 vs -2.00; -0.52 [-0.69, -0.35]; p <0.001 for UPA vs ABA). UPA also demonstrated superiority to ABA in achieving DAS28(CRP) <2.6 (30.0% vs 13.3%; p <0.001 for UPA vs ABA; Figure 1). Improvements in disease activity and remission rates were maintained through Wk 24. The proportions of pts achieving low disease activity (defined as DAS28(CRP) ≤3.2), ACR20, ACR50, and ACR70 responses were greater with UPA compared with ABA at Wk 12 (nominal p <0.05). More stringent outcome measures – CR, ACR50, and ACR70 responses - remained higher with UPA than ABA through Wk 24 (nominal p <0.05). Incidence of serious TEAEs, AEs leading to discontinuation, hepatic disorders, and CPK elevations were numerically higher with UPA versus ABA (Figure 2). Eight cases of herpes zoster were reported (4 in each treatment arm). No malignancies were reported. One case of adjudicated MACE, two adjudicated cases of VTE (1 pt with DVT and 1 pt with PE; both pts had at least one risk factor for VTE), and one treatment-emergent death were reported with UPA.Conclusion:In RA pts with a prior IR or intolerance to bDMARDs, UPA demonstrated superior improvement in signs and symptoms vs ABA based on change in DAS28(CRP) and in achieving CR at Wk 12. The safety profile of UPA was consistent with the phase 3 RA studies with no new risks identified.References:[1]Burmester GR, et al. Lancet. 2018;391(10139):2503-12[2]Fleischmann R, et al. Arthritis Rheumatol. 2019;71(11):1788-800[3]Genovese MC, et al. Lancet. 2018;391(10139):2513-24[4]Smolen JS, et al. Lancet. 2019;393(10188):2303-11Disclosure of Interests:Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Maureen Rischmueller Consultant of: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Nasser Khan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ying Zhang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Naomi Martin Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

scholarly journals SAT0411 EFFICACY AND SAFETY OF IXEKIZUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS AND INADEQUATE RESPONSE TO TNF INHIBITORS: THREE YEAR RESULTS FROM A PHASE 3 STUDY (SPIRIT-P2)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1158.1-1158
Author(s):  
J. Gratacos-Masmitja ◽  
A. Turkiewicz ◽  
E. Dokoupilova ◽  
A. M. Gellett ◽  
A. T. Sprabery ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Disease Activity ◽  
Outcome Measures ◽  
Signs And Symptoms ◽  
Severity Index ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Research Support ◽  
Intent To Treat

Background:Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets interleukin-17A. In the SPIRIT-P2 study, IXE every 4 (Q4W) or 2 (Q2W) weeks was superior to placebo (PBO) in improving the signs and symptoms of psoriatic arthritis (PsA) at Week 24 in patients (pts) with prior inadequate response or intolerance to 1 or 2 tumor necrosis factor inhibitors (TNFi).Objectives:To determine efficacy and safety of IXE treatment up to 3 years in pts with PsA.Methods:In SPIRIT-P2 (NCT02349295), 310 pts entered the extension period where pts maintained their original ixekizumab dose, and placebo pts received IXEQ4W or IXEQ2W (1:1). Pts failing to demonstrate ≥20% improvement in both tender and swollen joint counts at Week 32, or any subsequent visit, were discontinued (mandatory discontinuation criteria). Efficacy outcomes were ACR20/50/70 response, Psoriasis Area and Severity Index (PASI) 75/90/100 response, Leeds Enthesitis Index (LEI), Leeds Dactylitis Index-Basic (LDI-B), Minimal Disease Activity (MDA), and Disease Activity in Psoriatic Arthritis (DAPSA). Ad-hoc efficacy data are presented for intent-to-treat (ITT) pts initially randomized to IXE at Week 0. Observed and modified non-responder imputation (mNRI; missing data treated as non-response for pts discontinued due to lack of efficacy or adverse events [AEs]) was applied to categorical measures. Observed and modified baseline observation carried forward (mBOCF) was applied to continuous efficacy measures. Safety was analysed in pts exposed to at least one dose of IXE.Results:Of the 245 pts initially randomized to IXE at Week 0 (ITT), 64 (26.1%) pts discontinued due to lack of efficacy and 22 (9.0%) pts due to mandatory discontinuation criteria. Efficacy results are summarized below (Figure 1). Pts in SPIRIT-P2 who received IXEQ4W and IXEQ2W for 156 weeks reported sustained improvement in ACR responses and manifestations of PsA, including enthesitis, dactylitis, and skin outcomes. Treat-to-target measures such as MDA and DAPSA (Low Disease Activity or Remission) were achieved by 30.8% and 47.7% of pts, respectively on IXEQ4W, and by 29.2% and 40.7% of pts, respectively on IXEQ2W. Incidence rates (IR) of treatment-emergent adverse events (TEAEs) are provided below (Figure 2). Most TEAEs were mild or moderate in severity, and 38 out of 337 (5.9%) pts (safety population) discontinued due to AEs. The most common TEAEs were infections (IR=33.1) and injection site reactions (IR=5.4). Three deaths were reported in the study.Figure 1.Efficacy Outcome Measures at Week 156 (Intent-to-treat Population).ACR=American College of Rheumatology; IXE=ixekizumab; LEI=Leeds Enthesitis Index; LDI-B=Leeds Dactylitis Index-Basic; mNRI=modified non-responder imputation; PASI=Psoriasis Area and Severity Index; Q2W=every two weeks; Q4W=every four weeks.Figure 2.Safety Outcome Measures (Weeks 0-156).Safety was analysed in patients exposed to at least one dose of ixekizumab. During the double-blind treatment period (Weeks 0-24), one patient reported serious adverse events of anal fistula and anal abscess, which were considered by the sponsor to be IBD; however, an independent adjudication committee of external experts reviewed the case and determined the events to be “Not IBD.”Conclusion:In pts treated with IXE who had prior inadequate response or intolerance to 1 or 2 TNFi, improvements in the signs and symptoms of PsA persisted up to 3 years. No unexpected safety signals were observed, and the safety profile was consistent with previous studies of IXE.Disclosure of Interests:Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Anthony Turkiewicz Grant/research support from: Received research grants from AbbVie, Eli Lilly and Company, Janssen, Novartis, and Pfizer, Consultant of: Received consulting fees from AbbVie, Eli Lilly and Company, Janssen, Novartis, and Pfizer, Speakers bureau: On speaker bureau for Abbvie, Eli Lilly and Company, Janssen, Novartis, Pfizer, Eva Dokoupilova Grant/research support from: Eli Lilly, AbbVie, Novartis, Amanda M. Gellett Shareholder of: Eli Lilly and company, Employee of: Eli Lilly and company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Vladimir J. Geneus Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Arnaud Constantin Grant/research support from: Study was sponsored by Sanofi Genzyme, Consultant of: Consulting fees from Abbvie, BMS, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, UCB

scholarly journals OP0228 EFFICACY AND SAFETY OF IXEKIZUMAB VERSUS ADALIMUMAB (SPIRIT-H2H) WITH AND WITHOUT CONCOMITANT CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARD) IN BIOLOGIC DMARD-NAÏVE PATIENTS WITH PSORIATIC ARTHRITIS: 52-WEEK RESULTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 143-144 ◽  
Author(s):  
J. S. Smolen ◽  
A. Sebba ◽  
E. Ruderman ◽  
A. Gellett ◽  
C. Sapin ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Primary Endpoint ◽  
Severity Index ◽  
Current Treatment ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Research Support ◽  
Open Label ◽  
Biologic Dmards ◽  
Logistic Regression Models

Background:Ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting IL-17A, was superior to adalimumab (ADA) at Week (Wk) 24 for simultaneous achievement of ACR50 and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100) (primary endpoint) in patients (pts) with active PsA from SPIRIT-H2H1. SPIRIT-H2H had two major secondary endpoints and achieved both: noninferiority of IXE to ADA for ACR50 at Wk 24, and superiority of IXE to ADA for PASI 100 at Wk 24.Objectives:To determine how concomitant conventional synthetic DMARD (csDMARD) use affects safety and efficacy of IXE and ADA in prespecified subgroups defined by biologic monotherapy, concomitant MTX use, and concomitant csDMARD use through Wk 52 in SPIRIT-H2H.Methods:SPIRIT-H2H (NCT03151551) was a 52-week, multicentre, randomised, open-label, assessor-blinded, parallel-group study evaluating the efficacy and safety of IXE versus ADA in adults with PsA and naïve to biologic DMARDs. Patients were required to have active PsA fulfilling Classification for Psoriatic Arthritis (CASPAR) criteria and ≥3/68 tender and ≥3/66 swollen joints, ≥3% plaque psoriasis BSA involvement, no prior treatment with bDMARDs, and with prior inadequate response to ≥1 csDMARD (but not necessarily current treatment with csDMARDs). Randomization (1:1) was stratified by concomitant use of csDMARD and the presence/absence of moderate to severe PsO (baseline: BSA≥10% + PASI≥12, + static Physician’s Global Assessment≥3). Patients (N=566) received IXE/ADA through 52 wks according to the labelled dose dependent on presence/absence of moderate-to-severe PsO. In this prespecified subgroup analysis by presence or absence of csDMARDs, efficacy outcomes through wk 52 were compared between IXE and ADA using logistic regression models and Fisher’s exact tests. Missing data were imputed using non-responder imputation.Results:At baseline, 167 of 283 IXE-treated patients and 169 of 283 ADA-treated patients had concomitant MTX use. Of these, 9.0% (15/167) and 7.1% (12/169) treated with IXE and ADA, respectively, were taking an additional csDMARD (sulfasalazine, cyclosporine, or leflunomide). A significantly greater proportion of patients on IXE versus ADA achieved the primary endpoint or PASI 100 when used as monotherapy or in combination with csDMARD (Figure 1A and 1C). At Wk 52, the proportion of patients achieving ACR50 was not statistically different between IXE and ADA, regardless of monotherapy or concomitant csDMARD use (Figure 1B). A significantly higher proportion of patients achieved MDA on IXE compared to ADA in the monotherapy subgroup (49% vs 33%), while the response rates were similar in both combination subgroups (Figure 1D). These data support consistent ACR50, PASI 100, and MDA response for IXE across all three subgroups. Frequencies of adverse events were similar across the three subgroups for IXE and ADA (Figure 2).Conclusion:As with prior studies,2,3consistent efficacy across multiple PsA disease-specific endpoints was observed with IXE in SPIRIT-H2H, regardless of whether IXE was taken as monotherapy or in combination with MTX or another csDMARD. No unexpected safety signals were found for either agent.References:[1]Mease et al, Ann Rheum Dis 2020;79:123-31.[2]Coates et al, RMD Open 2017;3:e000567.[3]Nash et al, RMD Open 2018;4:e000692.Disclosure of Interests:Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Anthony Sebba Consultant of: Genentech, Gilead, Lilly, Regeneron Pharmaceuticals Inc., Sanofi, Speakers bureau: Lilly, Roche, Sanofi, Eric Ruderman Consultant of: Pfizer, Amanda Gellett Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Sreekumar Pillai Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Paulo Reis Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB

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