scholarly journals O23 Ixekizumab (IXE) vs. adalimumab (ADA) for the treatment of PSA: 52-week efficacy and safety outcomes

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Christopher J Edwards ◽  
Andrew J Bradley ◽  
Mani H Nassab ◽  
Burkhard Möller ◽  
Klaus P Machold ◽  
...  
Keyword(s):  
Severe Psoriasis ◽  
Tender Joint Count ◽  
Stock Ownership ◽  
Physician Global Assessment ◽  
Inadequate Response ◽  
Full Time ◽  
Research Support ◽  
Open Label ◽  
Tender Joint ◽  
Full Time Employee

Abstract Background With multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) available, comparisons are important for treatment decisions. At week 24 of the SPIRIT H2H study in patients with active PSA, IXE showed superiority to ADA for the simultaneous achievement of ACR50 and PASI100. Here we report the 52-week efficacy outcomes including individual ACR components and in subgroups +/- concomitant methotrexate (MTX). Methods SPIRIT H2H (NCT03151551) was a 52-week, multicentre, open-label, blinded-assessor study of bDMARD naïve patients with active PSA (defined as swollen joint count ≥3/68, and tender joint count ≥3/66), with a body surface area (BSA) ≥3% and inadequate response to conventional synthetic (cs)-DMARDs. Patients were randomised 1:1 to IXE or ADA stratified by concomitant csDMARD use and the presence of moderate-to-severe psoriasis (defined as Psoriasis Area and Severity Index [PASI] ≥12 combined with a static Physician Global Assessment ≥3 and BSA ≥10%). Patients received approved label dosing of assigned treatment dependent on presence/absence of moderate-to-severe psoriasis. Primary outcome was achievement of simultaneous ACR50 + PASI100; secondary outcomes were achievement of PASI100, ACR20/50/70 and changes in individual ACR component scores. Data were analysed using logistic regression with non-responder imputation for missing data. Results Baseline characteristics were balanced across treatment groups. At week 52, a significantly larger percentage of IXE- vs. ADA-treated patients achieved simultaneous ACR50 + PASI100 and PASI100, consistent with 24-week results (table). IXE performed at least as well as ADA at week 52 for all other outcomes (table). With/without MTX, IXE efficacy was consistent at week 52 across ACR20/50/70 with a significantly greater achievement of simultaneous ACR50 + PASI100 and ACR70 (table). IXE- versus ADA-treatment resulted in comparable changes from baseline for each individual ACR component at week 52. Safety was consistent with previous reports. Conclusion In patients with PSA, treatment with IXE versus ADA resulted in a significantly greater achievement of simultaneous skin and joint improvement at week 52, consistent with week 24 results. At week 52 consistent efficacy was shown for IXE when used with/without MTX. Disclosures C.J. Edwards: Consultancies; Celltrion, Abbvie, Samsung. Honoraria; Abbvie, BMS, Biogen, Chugai, Fresenius, Gilead, Janssen, Lilly, Pfizer, Roche, Samsung, UCB. Member of speakers’ bureau; Abbvie, BMS, Biogen, Chugai, Fresenius, Gilead, Janssen, Lilly, Pfizer, Roche, Samsung, UCB. Grants/research support; Pfizer, Biogen, Abbvie. A.J. Bradley: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. M.H. Nassab: Other; Full time employee of Eli Lilly. B. Möller: None. K.P. Machold: Honoraria; Arsanis, Astro, Baxter, BMS, Celgene, Eli-Lilly, MSD, Pfizer, Roche, Novartis, Sandoz. Member of speakers’ bureau; MSD, Pfizer, BMS, Janssen-Cilag, Sandoz, Novartis, Eli-Lilly. Grants/research support; AbbVie, BMS, Eli-Lilly, Novartis, MSD, Pfizer, Sanofi-Aventis, UCB. C. Sapin: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. R. Ranza: Consultancies; Abbvie, Novartis, Lilly, Pfizer, Janssen. Member of speakers’ bureau; Abbvie, Novartis, Lilly, Pfizer, Janssen. Grants/research support; Abbvie, Novartis, Pfizer, Janssen. S.L. Leage: Other; Full time employee of Eli Lilly.

scholarly journals P276 Comparative effects of ixekizumab (IXE) vs adalimumab (ADA) across PsA patients defined by baseline characteristics: week 24 outcomes from SPIRIT-H2H

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Hasan Tahir ◽  
Andrew J Bradley ◽  
Mani H Nassab ◽  
Burkhard Möller ◽  
Josef S Smolen ◽  
...  
Keyword(s):  
Comparable Efficacy ◽  
Tender Joint Count ◽  
Stock Ownership ◽  
Physician Global Assessment ◽  
Full Time ◽  
Tnf Inhibitor ◽  
Open Label ◽  
Tender Joint ◽  
Full Time Employee ◽  
Post Hoc

Abstract Background Comparisons of PsA treatment options to guide physicians are limited. When conventional treatment is insufficient, the recommendations is a biological agent, most frequently tumour necrosis factor (TNF)-inhibitors. IXE, an IL-17A antagonist biologic, showed superiority over TNF-inhibitor ADA for the simultaneous achievement of ACR50 and PASI100, and PASI100 alone in the SPIRIT-H2H trial at week 24. We analysed differences in efficacy outcomes between IXE and ADA by subgroups based on baseline clinical characteristics. Methods We conducted post-hoc analysis of data from SPIRIT-H2H (NCT03151551), a 52-week, multicentre, open-label, blinded assessor study patients with active PsA (defined as swollen joint count ≥3 and tender joint count ≥3), with a body surface area (BSA) ≥3% and insufficient response to ≥ 1 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and naïve to biologic (b)-DMARDs. Patients were randomised 1:1 to IXE or ADA, while presence/absence of moderate-to-severe psoriasis (defined as PASI ≥12, static Physician Global Assessment ≥3 and BSA ≥10%) determined on-label dosing. Subgroups were defined by baseline enthesitis, dactylitis, fingernail psoriasis (presence/absence), BSA (<10%, ≥10%) and CRP (≤6 mg/L,>6 mg/L). A Fisher’s exact test was used for between group comparisons of efficacy outcome measures at 24 weeks (PASI90, ACR50/70, and minimal disease activity [MDA]). Missing data were overcome by non-responder imputation. Results At week 24, IXE and ADA demonstrated comparable efficacy in ACR50 response rates across all subgroups. ACR70 response in patients with fingernail psoriasis was significantly greater with IXE-treated vs ADA (p = 0.02) (table). PASI90 response with baseline enthesitis (p < 0.001), without dactylitis (p < 0.001), with fingernail psoriasis (p < 0.001), CRP (≤6 mg/L, p = 0.003; >6 mg/L, p = 0.036) and BSA (<10%, p = 0.010; ≥10%, p = 0.003) was significantly greater in IXE vs ADA (table). Significantly more IXE-treated patients vs ADA achieved MDA with baseline enthesitis (p = 0.002), without dactylitis (p = 0.015), with fingernail psoriasis (p < 0.001), CRP ≤6 mg/L (p = 0.046) and BSA ≥10% (p = 0.01) (table). A limitation is that this analysis was completed post-hoc, not controlled for multiplicity, and patients were not stratified by baseline disease characteristics. Conclusion IXE and ADA are associated with comparable efficacy and associated with a greater effect in certain subgroups. Results will aid clinicians when making treatment choices. Disclosures H. Tahir: Consultancies; Novartis, Eli-Lilly, Abbvie. A.J. Bradley: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. M.H. Nassab: Other; Full time employee of Eli Lilly. B. Möller: None. J.S. Smolen: Consultancies; AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Medimmune, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB. Grants/research support; AbbVie, Eli Lilly, Novartis, Pfizer, Roche. C. Sapin: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. C.F. Dionello: Consultancies; Novartis, Lilly, Janssen, Abbvie. Honoraria; Novartis, Lilly, Janssen, Abbvie, Roche, Pfizer. G. Meszaros: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly.

scholarly journals P204 Effect of baricitinib on functional impairment in RA patients with moderate disease activity and an inadequate response to conventional DMARDs

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Bruce Kirkham ◽  
Elena Nikiphorou ◽  
Pedro López-Romero ◽  
Ilias Kouris ◽  
Thorsten Holzkaemper ◽  
...  
Keyword(s):  
Disease Activity ◽  
Physical Function ◽  
Stock Ownership ◽  
Inadequate Response ◽  
Full Time ◽  
Research Support ◽  
Moderate Disease ◽  
Conventional Dmards ◽  
Full Time Employee ◽  
Moderate Disease Activity

Abstract Background In RA, disease activity correlates with physical function and there is a link between joint damage and functional disability. In many countries, RA patients with inadequate response (IR) to MTX or other conventional DMARDs (cDMARDs) are not eligible for potentially more effective treatments, such as biologic or targeted synthetic DMARDs (tsDMARDs), unless they have high disease activity (HDA). Thus, managing RA patients with persistent moderate disease activity (MDA) despite cDMARD treatment poses a problem. Baricitinib (BARI) is a tsDMARD approved for the treatment of moderate to severe RA in adults. This post-hoc analysis assessed if RA patients with MDA benefit from improved physical function with BARI treatment to the same extent as patients with HDA. Methods Patients analysed were from the modified intention-to-treat populations in the BARI phase 3 studies RA-BEAM (MTX-IR) and RA-BUILD (cDMARD-IR) with moderate to severe disability (HAQ-Disability Index [HAQ-DI] score ≥1), MDA (Simplified Disease Activity Index [SDAI] score 11.1-26.0) or HDA (SDAI score>26.0) and non-missing SDAI data at baseline. All patients fulfilled ACR criteria for RA. Patients from RA-BEAM received BARI 4 mg + MTX once daily (n = 396), adalimumab 40 mg every 2 weeks + MTX (n = 270) or placebo (PBO) + MTX (n = 390); patients from RA-BUILD received BARI 4 mg (n = 189) or 2 mg (n = 186) or PBO (n = 185). Multivariable linear regression (MLR) models were used to estimate mean HAQ-DI scores at baseline and week 24 (W24) for the treatment arms stratified by baseline disease activity (MDA or HDA SDAI). Age, RA duration, BMI, high-sensitivity CRP, baseline SDAI disease activity (MDA/HDA), treatment and treatment-by-baseline SDAI interaction were included as covariates. The MLR model for HAQ-DI at (W24) was further adjusted by baseline HAQ-DI. Results In patients from RA-BEAM with MDA at baseline, the mean adjusted HAQ-DI score at W24 was greater in PBO (1.314) than in BARI 4 mg (0.843) patients (Δ = 0.472; p = 0.001). A similar pattern of improved physical function with BARI was seen in RA-BUILD, but the adjusted mean difference in HAQ-DI score between PBO (1.376) and BARI 4 mg (1.113) was not statistically significant (Δ = 0.263; p = 0.109). In patients with HDA at baseline, the W24 mean adjusted HAQ-DI score was 0.443 points greater (p < 0.001) with PBO (1.387) than with BARI 4 mg (0.944) in RA-BEAM, and 0.257 points greater (p < 0.001) in RA-BUILD. Conclusion MTX-IR and/or cDMARD-IR RA patients with MDA and moderate to severe disability at baseline treated with BARI showed a similar pattern of improvement in physical function vs. PBO-treated patients to that seen in patients with HDA, supporting early use of BARI in MDA patients. As for those with HDA, patients with persistent MDA despite MTX and/or other cDMARD treatment could benefit from access to biologic and tsDMARDs to prevent disability progression. Disclosures B. Kirkham: Consultancies; AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer. Grants/research support; Eli Lilly, Novartis. E. Nikiphorou: Honoraria; Pfizer, Sanofi, Gilead, Celltrion, Eli Lilly. P. López-Romero: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. I. Kouris: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. T. Holzkaemper: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. L. Zaremba-Pechmann: Other; contractor for Eli Lilly and Company. I. de la Torre: Shareholder/stock ownership; Eli Lilly. Other; Full time employee of Eli Lilly. P.C. Taylor: Consultancies; AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Roche, Sanofi, Nordic Pharma, Fresenius, UCB. Grants/research support; Celgene, Galapagos, Janssen, Eli Lilly.

scholarly journals P192 Secukinumab provides rapid and sustained improvements in subgroup analyses of joint tenderness and swelling in patients with psoriatic arthritis: 2-year results from the Phase 3 FUTURE 5 study

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Iain McInnes ◽  
Hector Chinoy ◽  
Darren Asquith ◽  
Abigail White ◽  
Corine Gaillez
Keyword(s):  
Psoriatic Arthritis ◽  
Total Population ◽  
Population Change ◽  
Tender Joint Count ◽  
Stock Ownership ◽  
Inadequate Response ◽  
Tender Joint ◽  
Acr20 Response ◽  
Response Versus ◽  
Necrosis Factor

Abstract Background/Aims  We report the 2-year effects of secukinumab on 78 tender joint count (TJC)/76 swollen joint count (SJC) scores in key subgroups of FUTURE 5: patients naive/with prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFis), and patients with/without concomitant methotrexate (MTX) use. Methods  996 patients with active psoriatic arthritis, who received ≤3 prior TNFis and/or concomitant MTX, were randomised to secukinumab 300 or 150 mg with loading dose (LD), 150 mg without LD or placebo. Treatments were given at baseline, Weeks 1-4 and every 4 weeks thereafter. Placebo-treated patients were re-randomised to secukinumab 300/150 mg at Week 16 (non-responders) or 24 (responders). Secukinumab dose could be escalated from 150 to 300 mg from Week 60 and maintained thereafter. ACR20 response and changes in 78 TJC/76 SJC are reported over 2 years in TNFi-naive/IR and with/without concomitant MTX subgroups. Results  The primary endpoint, ACR20 response at Week 16, is reported elsewhere. At Week 104, 78.1%, 81.8% and 80.8% of TNFi-naive patients achieved an ACR20 response versus 74.0%, 72.1% and 69.8% of TNFi-IR patients with secukinumab 300, 150 and 150 mg no LD, respectively. At the same timepoint, 76.5%, 80.2% and 78.3% of patients with concomitant MTX achieved an ACR20 response versus 77.6%, 78.6% and 77.6% of patients without concomitant MTX with secukinumab 300, 150 and 150 mg no LD, respectively. At Week 104, mean change from baseline in adjusted 78 TJC/76 SJC scores for TNFi-naive and TNFi-IR patients was -14.1/-8.6 and -19.0/-9.1 for secukinumab 300 mg, -15.7/-9.6 and -19.1/-12.2 for secukinumab 150 mg, and -17.7/-10.9 and -17.9/-9.9 for secukinumab 150 mg no LD, respectively (Table 1). At Week 104, mean change from baseline in adjusted 78 TJC/76 SJC scores for patients with and without concomitant MTX was -15.7/-8.5 and -15.1/-3.4 for secukinumab 300 mg, -16.4/-10.4 and -16.8/-10.1 for secukinumab 150 mg, and -17.0/-10.3 and -18.6/-11.1 for secukinumab 150 mg no LD, respectively. Conclusion  Secukinumab provided rapid improvements in TJC and SJC at Week 16, which were sustained through Week 104, irrespective of TNFi history/concomitant MTX use. P192 Table 1:Selected baseline characteristics and 78 TJC and 76 SJC Results at Week 104Selected baseline characteristicsVariableSEC 300 mg (N = 222)SEC 150 mg (N = 220)SEC 150 mgno LD (N = 222)PBO (N = 332)Mean adjusted 78 TJC scoreTotal population19.821.221.821.2Mean adjusted 76 SJC scoreTotal population10.012.111.911.778 TJC and 76 SJC Results at Week 104EndpointSECPBO-SEC300 mg SC(N = 100)150 mg SCa(N = 100)150 mg SCno LDb(N = 222)300 mg SC (N = 153)150 mgc (N = 153)Adjusted 78 TJC (total population)Change from baseline (SD)-15.4 (12.5)-16.6 (14.3)-17.7 (15.3)-17.2 (14.9)-15.2 (13.0)Adjusted 76 SJC (total population)Change from baseline (SD)-8.7 (7.3)-10.3 (10.5)-10.6 (9.6)-10.7 (10.0)-9.6 (9.2)Adjusted 78 TJC (TNF status)TNFi-naiveChange from baseline (SD)-14.1 (11.6)-15.7 (14.1)-17.7 (15.0)-16.6 (13.7)-14.5 (12.6)TNFi-IRChange from baseline (SD)-19.0 (14.3)-19.1 (14.7)-17.9 (16.3)-18.9 (18.1)-17.6 (14.5)Adjusted 76 SJC (TNF status)TNFi-naiveChange from baseline (SD)-8.6 (7.2)-9.6 (9.6)-10.9 (10.1)-10.5 (8.6)-9.2 (7.5)TNFi-IRChange from baseline (SD)-9.1 (7.8)-12.2 (12.8)-9.9 (7.9)-11.0 (13.4)-10.9 (13.4)Adjusted 78 TJC (MTX use)Concomitant MTX useChange from baseline (SD)-15.7 (12.3)-16.4 (14.7)-17.0 (14.0)-17.8 (16.0)-15.8 (14.2)No concomitant MTX useChange from baseline (SD)-15.1 (12.8)-16.8 (13.9)-18.6 (16.8)-16.4 (14.0)-14.7 (12.1)Adjusted 76 SJC (MTX use)Concomitant MTX useChange from baseline (SD)-8.5 (5.9)-10.4 (11.1)-10.3 (8.6)-10.7 (9.6)-8.9 (7.8)No concomitant MTX useChange from baseline (SD)-8.9 (8.7)-10.1 (10.0)-11.1 (10.8)-10.6 (10.6)-10.1 (10.2)aIncludes 76 patients who were uptitrated to SEC 300 mg starting at Week 60;bIncludes 77 patients who were uptitrated to SEC 300 mg starting at Week 60;cIncludes 52 patients who were uptitrated to SEC 300 mg starting at Week 60. Data are reported as observed. N=number of randomised patients; n=number of patients with evaluation. IR, inadequate response; LD, loading dose; MTX, methotrexate; PBO, placebo; PsA, psoriatic arthritis; SD, standard deviation; SEC, secukinumab; SJC, swollen joint count; TJC, tender joint count; TNFi, tumour necrosis factor inhibitor. Disclosure  I. McInnes: Grants/research support; AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. H. Chinoy: Grants/research support; AbbVie, Amgen, Biogen, BMS, Janssen, Lilly, Novartis, UCB. D. Asquith: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Shareholder of Novartis. A. White: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Shareholder of Novartis. C. Gaillez: Corporate appointments; Employee of Novartis. Shareholder/stock ownership; Shareholder of Novartis and Bristol Myers Squibb.

scholarly journals O09 Pooled safety analyses from Phase 3 studies of filgotinib in patients with RA

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
David Walker ◽  
Kevin Winthrop ◽  
Mark C Genovese ◽  
Bernard G Combe ◽  
Yoshiya Tanaka ◽  
...  
Keyword(s):  
Safety Data ◽  
Study Drug ◽  
Janus Kinase ◽  
Tender Joint Count ◽  
Stock Ownership ◽  
Tolerability Profile ◽  
Inadequate Response ◽  
Control Groups ◽  
Research Support ◽  
Phase 3

Abstract Background Filgotinib (FIL) is an oral, selective janus kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, summarized, summarized studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24). Methods The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to standard of care. W24 safety data from all studies were aggregated and ummarized. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities. Results 3,452 patients were evaluated; 2,088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups. Conclusion Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD. Disclosures D. Walker: Other; Received support from Lilly, Pfizer, Novartis and Roche. K. Winthrop: Grants/research support; Received grants for clinical research from Bristol-Myers Squibb Company and Insmed Incorporated. Other; Received support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly & Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, and UCB. M.C. Genovese: Other; Gilead Sciences Inc., Galapagos NV, AbbVie Inc. Eli Lilly and Company, Pfizer. B.G. Combe: Honoraria; Honoraria from AbbVie, BMS, Gilead, Janssen, Eli Lilly and Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. Y. Tanaka: Honoraria; Received from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly and Co., Pfizer, AbbVie, YL Biologics, BMS, Takeda, Misubishi-Tanabe, Novartis, Eisai, Janssen, Teijin. Grants/research support; Received grant support from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, BMS, UCB, Daiichi-Sankyo, Eisai, and Ono. A. Kivitiz: Consultancies; Consultant for AbbVie, Celgene, Horizon, Janssen, Merck, Novartis, Pfizer, UCB, Genzyme,Sanofi, Regeneron, SUN Pharma Advanced Research, Boehringer Ingelheim and Flexion. Shareholder/stock ownership; Shareholder of Novartis. 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; Gilead Sciences, Inc. Shareholder/stock ownership; 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. E. Keystone: Consultancies; 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 Samsung Bioepsis, and UCB. Other; 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. R. Westhovens: Corporate appointments; An investigator and advisor for Celltrion and Galapagos/Gilead. W. Rigby: Consultancies; Consultancy for Gilead. G.R. Burmester: Consultancies; Consultancy from AbbVie, Gilead, Eli Lilly, and Pfizer. Honoraria; Honoraria from AbbVie, Gilead, Eli Lilly, and Pfizer.

scholarly journals P196 Secukinumab provides sustained improvements in subgroup analyses of joint tenderness and swelling in patients with psoriatic arthritis: 5year results from the Phase3 FUTURE 2 study

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Iain McInnes ◽  
Hector Chinoy ◽  
Darren Asquith ◽  
Abigail White ◽  
Corine Gaillez
Keyword(s):  
Psoriatic Arthritis ◽  
Population Change ◽  
Tender Joint Count ◽  
Stock Ownership ◽  
Inadequate Response ◽  
Tender Joint ◽  
Acr20 Response ◽  
Joint Tenderness ◽  
Future 2 ◽  
Support Research

Abstract Background/Aims  We report the 5-year efficacy of secukinumab, an anti-interleukin17A inhibitor with long-term efficacy and tolerability in patients with psoriatic arthritis (PsA), on reduction of 78 tender joint count (TJC)/76 swollen joint count (SJC) scores in key subgroups of FUTURE 2: patients naive/with a prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFis), and patients with/without concomitant methotrexate (MTX) use. Methods  397 patients with active PsA, who received ≤3 prior TNFis and/or concomitant MTX, were randomised to secukinumab (300, 150, 75 mg) or placebo at baseline, Weeks 1-4, and every 4 weeks thereafter. Placebo-treated patients were rerandomised to secukinumab 300 or 150 mg at Week 16 (nonresponders) or 24 (responders). Secukinumab dose could be escalated from 150 to 300 mg or from 75 to 150/300 mg following physician’s assessment from Week 128 and maintained thereafter. ACR20 response and changes in 78 TJC/76 SJC are reported over 5 years for secukinumab 300 and 150 mg (approved PsA doses) in TNFi-naive/IR and with/without concomitant MTX subgroups. Results  The primary endpoint, ACR20 response at Week 24, is reported elsewhere. In the secukinumab 300 and 150 mg arms, 79.6% and 77.1% of TNFinaive patients achieved an ACR20 response versus 56.3% and 66.7% of TNFi-IR patients at Week 260. At the same timepoint, 62.5% and 73.5% of patients with concomitant MTX use achieved an ACR20 response versus 84.8% and 75.0% of patients without concomitant MTX use in the secukinumab 300 and 150 mg arms, respectively. At Week 260, mean change from baseline in adjusted 78 TJC/76 SJC scores for TNFi-naive and TNFi-IR patients was −13.1/−9.5 and −12.0/−8.9 for secukinumab 300 mg and −15.3/−8.8 and −14.4/−7.9 for secukinumab 150 mg, respectively (Table 1). At Week 260, mean change from baseline in adjusted 78 TJC/76 SJC scores for patients with and without concomitant MTX was −11.2/−8.9 and −14.4/−9.7 for secukinumab 300 mg and −14.7/−9.5 and −15.4/−7.5 for secukinumab 150 mg, respectively. P196 Table 1:Selected baseline characteristics and 78 TJC and 76 SJC results at Week 24 and Week 260Selected baseline characteristicsVariableSEC 300 mg SC(N = 100)SEC 150 mg SC (N = 100)PBO (N = 98)Mean adjusted 78 TJC scoreTotal population20.224.123.4Mean adjusted 76 SJC scoreTotal population11.211.912.178 TJC and 76 SJC results at Week 24 and Week 260EndpointWeek 24Week 260SEC300 mg SC (N = 100)SEC150 mg SC (N = 100)PBO-SEC300 mg SC (N = 45)PBO-SEC150 mg (N = 43)SEC300 mg SC (N = 100)SEC150 mg SCa (N = 100)PBO-SEC 300 mg SC (N = 45)PBO-SEC 150 mgb (N = 43)Adjusted 78 TJC (total population)Change from baseline (SD)−10.4 (10.8)−12.1 (16.5)−10.6 (14.1)−9.7 (13.6)−12.8 (10.7)−15.1 (15.9)−14.5 (15.4)−12.5 (10.6)Adjusted 76 SJC (total population)Change from baseline (SD)−7.2 (5.8)−6.3 (7.7)−9.7 (9.5)−9.6 (10.7)−9.3 (6.1)−8.5 (7.9)−9.5 (8.1)−8.3 (6.3)Adjusted 78 TJC (TNF status)TNFi-naiveChange from baseline (SD)−10.7 (10.8)−13.0 (16.6)−3.5 (13.9)−8.0 (10.7)−13.1 (11.1)−15.3 (16.7)−14.8 (16.0)−11.5 (10.2)TNFi-IRChange from baseline (SD)−9.8 (10.9)−10.3 (16.4)−11.0 (11.4)−13.4 (19.5)−12.0 (9.6)−14.4 (14.0)−14.0 (15.1)−15.7 (12.0)Adjusted 76 SJC (TNF status)TNFi-naiveChange from baseline (SD)−6.9 (4.8)−6.7 (8.2)−10.5 (11.0)−6.8 (6.2)−9.5 (5.7)−8.8 (8.8)−9.4 (9.0)−8.4 (6.9)TNFi-IRChange from baseline (SD)−7.8 (7.4)−5.7 (6.5)−7.8 (5.0)−15.6 (16.3)−8.9 (7.4)−7.9 (5.1)−9.6 (6.1)−7.9 (4.6)Adjusted 78 TJC (MTX use)Concomitant MTX useChange from baseline (SD)−10.3 (8.7)−10.6 (16.7)−8.7 (13.1)−7.6 (14.3)−11.2 (9.1)−14.7 (14.5)−12.7 (12.5)−11.4 (11.4)No concomitant MTX useChange from baseline (SD)−10.5 (12.3)−13.3 (16.4)−15.2 (16.8)−14.2 (12.0)−14.4 (12.0)−15.4 (17.5)−16.8 (18.6)−14.1 (9.6)Adjusted 76 SJC (MTX use)Concomitant MTX useChange from baseline (SD)−6.9 (6.1)−6.0 (8.5)−8.9 (8.6)−8.8 (9.7)−8.9 (6.0)−9.5 (9.1)−8.6 (5.3)−9.4 (7.2)No concomitant MTX useChange from baseline (SD)−7.4 (5.7)−6.6 (6.9)−11.6 (12.4)−11.2 (13.8)−9.7 (6.2)−7.5 (6.5)−10.6 (10.7)−6.6 (4.6)aSEC 150 mg arm includes 42 patients who were uptitrated to SEC 300 mg from Week 128.bPBO-SEC 150 mg arm includes 19 patients who were uptitrated to SEC 300 mg from Week 128. Data are reported as observed.N=number of randomised patients; n=number of patients with evaluation. IR, inadequate response; MTX, methotrexate; PBO, placebo; PsA, psoriatic arthritis; SC, subcutaneous; SD, standard deviation; SEC, secukinumab; SJC, swollen joint count; TJC, tender joint count; TNFi, tumour necrosis factor inhibitor. Conclusion  Analysis of 78 TJC/76 SJC scores demonstrated that treatment with secukinumab significantly reduced joint tenderness and swelling at Week 24, which were sustained over 5 years, irrespective of TNFi history/concomitant MTX use. Disclosure  I. McInnes: Grants/research support; Research grants, consultation fees, or speaker honoraria: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. H. Chinoy: Grants/research support; Research grants, travel grants, consultancy or speaker honoraria: AbbVie, Amgen, Biogen, BMS, Janssen, Lilly, Novartis and UCB. D. Asquith: Shareholder/stock ownership; Employee of Novartis. Shareholder of Novartis. A. White: Shareholder/stock ownership; Employee of Novartis. Shareholder of Novartis. C. Gaillez: Shareholder/stock ownership; Employee of Novartis. Shareholder of Novartis and Bristol Myers Squibb.

scholarly journals EP25 Impact of sarilumab on unacceptable pain and inflammation control in moderately-to-severely active rheumatoid arthritis (RA) patients in 3 Phase 3 studies

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Vivian Bykerk ◽  
Wenhui Wei ◽  
Susan Boklage ◽  
Toshio Kimura ◽  
Stefano Fiore ◽  
...  
Keyword(s):  
Health Assessment ◽  
Tender Joint Count ◽  
Stock Ownership ◽  
Inadequate Response ◽  
Tender Joint ◽  
Lower Odds ◽  
Reactive Protein ◽  
Refractory Pain ◽  
Randomised Controlled ◽  
Post Hoc

Abstract Background In RA patients, unacceptable pain (UP) may persist despite inflammation control (refractory pain [RP]). Sarilumab is indicated (either with methotrexate or as monotherapy if methotrexate is not tolerated/appropriate) for adults with moderately-to-severely active RA with an inadequate response or intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatics (csDMARD). The recommended dose is 200 mg every 2 weeks (q2w) with dose reduction to 150 mg if required for management of laboratory abnormalities. Three randomised controlled trials (RCTs) of subcutaneous sarilumab 150 or 200 mg q2w vs comparators showed meaningful improvements in pain. This analysis assessed UP and RP in these trials. Methods RCTs evaluated sarilumab 150 and 200 mg q2w vs placebo (+csDMARDs: MOBILITY/NCT01061736 and TARGET/NCT01709578) and sarilumab 200 mg q2w vs adalimumab 40 mg q2w (MONARCH/NCT02332590). Post-hoc analyses calculated odds ratios (ORs) of UP (based on patient acceptable symptom state on a threshold of visual analog scale pain >40 mm [0-100]), RP (UP+C-reactive protein <10 mg/L), and RP-strict (RP + ≤1 swollen joint count [SJC]), and associations between pain and fatigue (FACIT-Fatigue) and disease activity (Health Assessment Questionnaire [HAQ], SJC and tender joint count [TJC]). P values are nominal. Results Across all three trials, sarilumab 150 and 200 mg q2w had lower odds of UP (p < 0.05; ORs 0.39-0.46 vs placebo and 0.54 vs adalimumab). In MOBILITY, sarilumab 150 and 200 mg q2w had lower odds (p < 0.05) of RP vs placebo at Week 24 (ORs 0.60 [0.38,0.93] and 0.57 [0.37,0.87]) and Week 52 (ORs 0.64 [0.37,1.02] and 0.62 [0.37,1.02]), and RP-strict at Week 52 (0.41 [0.19,0.90] and 0.35 [0.16,0.76]). In TARGET, sarilumab 150 mg q2w had lower odds (p < 0.05) of RP-strict at Week 24. Higher pain was associated with worse FACIT-fatigue, HAQ, SJC and TJC scores (all p < 0.001). Conclusion Sarilumab was associated with lower odds of UP or RP vs adalimumab or placebo. Disclosures V. Bykerk: Consultancies; Abbvie, Amgen, Brainstorm Therapeutics, Bristol-Myers Squibb, Genentech, Gilead, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Scipher, Union Chimique Belge. Shareholder/stock ownership; Abbvie, Amgen, Brainstorm Therapeutics, Bristol-Myers Squibb, Genentech, Gilead, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Scipher, Union Chimique Belge. Grants/research support; AbbVie, Amgen, Brainstorm Therapeutics, Bristol-Myers Squibb, Genentech, Gilead, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Scipher, Union Chimique Belge. W. Wei: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc. S. Boklage: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc. T. Kimura: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc. S. Fiore: Shareholder/stock ownership; Sanofi. Other; Sanofi. G. St John: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc.

FRI0332 EVALUATION OF THE INDIVIDUAL COMPONENTS OF ACR50+PASI100 AND MDA AT WEEK 24 FROM THE SPIRIT-H2H TRIAL COMPARING THE EFFICACY AND SAFETY OF IXE VERSUS ADA IN PATIENTS WITH PSA NAÏVE TO BDMARDS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 758.1-758
Author(s):  
L. C. Coates ◽  
M. Nissen ◽  
C. El Baou ◽  
J. Zochling ◽  
A. Marchesoni ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Rheumatic Diseases ◽  
Task Force ◽  
Systemic Disease ◽  
Tender Joint Count ◽  
Efficacy And Safety ◽  
Research Support ◽  
Open Label ◽  
Tender Joint ◽  
The Individual

Background:Psoriatic arthritis (PsA) is a chronic systemic disease with manifestations affecting musculoskeletal and extra-articular domains. Treatment and assessment of response are therefore major challenges in routine clinical practice. Minimal disease activity (MDA) is a multidimensional endpoint that can define a treatment target1. In SPIRIT-H2H2, a head-to-head clinical trial comparing the efficacy and safety of ixekizumab (IXE) versus) to adalimumab (ADA), the percentage of patients simultaneously achieving American College of Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI100), was the primary endpoint in order to reflect improvement in two domains of PsA.Objectives:To evaluate how individual components of the simultaneous achievement of ACR50 and PASI100 compare with those of MDA at week 24.Methods:Patients with active PsA (defined as those with a tender joint count [TJC] ≥ 3/68, a swollen joint count [SJC] ≥ 3/66 and a body surface area [BSA] of active plaque psoriasis ≥ 3%) were randomised 1:1 to approved dosing (according to baseline psoriasis involvement) of IXE or ADA in SPIRIT-H2H, an open label, assessor-blinded study.The proportion of patients meeting each criterion of the composite endpoints was calculated for the intent-to-treat ([ITT], N=566) population and the population of MDA responders at Week 24 (N=235). Missing individual responses were imputed with non-responder status. Spidergrams were generated using SAS 9.4.Results:For both the overall ITT population and the MDA responders population, the use of PASI≤1 or BSA≤3% in the skin-related component of the MDA contributed to the higher response rate relative to the PASI100 response. Thus, the PASI100 response is a more stringent endpoint. Proportions of responders are similar across MDA and ACR50+PASI100 individual components for HAQ and SJC. The high baseline TJC levels (mean TJC: IXE=19.1, ADA=21.3) as opposed to lower levels observed for baseline SJC (mean SJC: IXE=10.1, ADA=10.7) made MDA-TJC criterion (≤1) more difficult to achieve than the equivalent criterion of the ACR50+PASI100 endpoint.Conclusion:Despite the differences in criteria definitions, there are consistent response patterns in the individual components of the simultaneous ACR50+PASI100 and MDA endpoints in particular for the peripheral arthritis domain.References:[1]Smolen, Josef S et al. “Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force.”Annals of the rheumatic diseasesvol. 77,1 (2018): 3-17.[2]Mease PJ The SPIRIT H2H study group, et al. “A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial.”Annals of the Rheumatic Diseases2020;79:123-131.Disclosure of Interests:Laura C Coates: None declared, Michael Nissen Grant/research support from: Abbvie, Consultant of: Novartis, Lilly, Abbvie, Celgene and Pfizer, Speakers bureau: Novartis, Lilly, Abbvie, Celgene and Pfizer, Celine El Baou Consultant of: Eli Lilly and Company, Jane Zochling Employee of: Jannssen Cilag, Speakers bureau: Janssen Cilag, AbbVie, Novartis, UCB, BMS, Eli Lilly, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Enrique Soriano Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc, Sandoz, Consultant of: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc, Sandoz, Speakers bureau: AbbVie, Amber, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer Inc, Roche, Valderilio F Azevedo Grant/research support from: Abbvie, Janssen, Bristol-Myers Squibb, Boehringer-Ingelheim, Lilly and Novartis, Consultant of: Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Speakers bureau: Sandoz, Celltrion, Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Klaus Machold Grant/research support from: AbbVie, MSD, UCB, Consultant of: Arsanis, Astro, Baxter, BMS, Celgene, Eli-Lilly, MSD, Pfizer, Roche, Novartis, Sandoz, Speakers bureau: MSD, Pfizer, BMS, Janssen-Cilag, Sandoz, Novartis, Eli-Lilly, Christophe Sapin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company

scholarly journals OP0252 CIRCULATING COLLAGEN TURNOVER MARKERS ARE SPECIFICALLY CHANGED IN VERY EARLY SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 159.1-159
Author(s):  
R. Dobrota ◽  
S. Jordan ◽  
P. Juhl ◽  
B. Maurer ◽  
M. O. Becker ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Roc Analysis ◽  
Cox Regression ◽  
Classification Criteria ◽  
Full Time ◽  
Research Support ◽  
Type Iii ◽  
Turnover Markers ◽  
Full Time Employee

Background:Timely diagnosis of patients with very early systemic sclerosis (veSSc) is essential for their personalized and optimal management. We hypothesise that changes in serum-based extracellular matrix (ECM) turnover biomarkers are already detectable in patients with veSSc, even before occurrence of specific clinical signs.Objectives:To investigate circulating ECM turnover markers as potential biomarkers for veSSc.Methods:Patients with veSSc, n=42, defined as presence of Raynaud’s syndrome and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, who did not meet any classification criteria for SSc, were compared to healthy controls (HC, n=29). Longitudinal assessment, data and sera collection were conducted by EUSTAR standards. ECM-degradation (BGM, C3M, C4M, C6M) and ECM-formation biomarkers (PRO-C3, PRO-C4, PRO-C5) were measured in serum using ELISA assays. The statistical analyses included Mann-Whitney U, Spearman correlation and ROC analysis. Using Kaplan-Meier plots and univariable Cox regression, we explored if biomarkers can predict progression towards definite SSc (fulfillment of ACR/EULAR criteria or minimum two points increase in the criteria score) during the longitudinal follow-up.Results:Compared to HC, veSSc patients showed a deregulated turnover of type III and IV collagen, with higher degradation (higher C3M, C4M, both p<0.0001 and PRO-C3, p=0.004, Figure 1a, resulting in lower turnover ratios PRO-C3/C3M and PRO-C4/C4M, both p<0.0001). The biglycan degradation biomarker BGM was also higher in veSSc (p=0.006), whereas the degradation biomarker for type VI collagen, C6M, was lower than in HC (p=0.002). In the ROC analysis, biomarkers of type III and IV collagen distinguished between veSSc and HC: C3M, AUC=0.95, p<0.0001; C4M, AUC=0.97, p<0.0001; turnover ratios PRO-C3/C3M, AUC=0.80, p<0.0001; PRO-C4/C4M, AUC=0.97; p<0.0001 (Figure 1b).Median follow up was 4.5 years (range 0.5-7.9 years), mean age was 50±2.2 years, 88% female gender, 24% with puffy fingers, 92% were ANA positive, 64% had an abnormal capillaroscopy, none had organ involvement or skin fibrosis. 14/42 veSSc patients fulfilled the ACR/EULAR classification criteria at follow-up (time to fulfilment of criteria ranged between 0.5 and 6.8 years from inclusion) and in addition, 18/42 veSSc patients gained at least two classification criteria-points. This resulted in 14, respectively 18 progressors for the longitudinal analysis. However, in univariable Cox regression, the baseline levels of the markers did not predict progression over time.Conclusion:ECM turnover is already altered in veSSc patients compared to HC. Biomarkes of type III and IV collagen distinguished between veSSc patients and HC, which may indicate them as potential biomarkers for the detection of veSSc in addition to the established immunological and capillaroscopic criteria.Disclosure of Interests:Rucsandra Dobrota: None declared, Suzana Jordan: None declared, Pernille Juhl Employee of: Nordic Bioscience, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis, Mike O. Becker: None declared, Carina Mihai: None declared, Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Full time employee at Nordic Bioscience A/S., Morten Karsdal Shareholder of: Nordic Bioscience A/S., Employee of: Full time employee at Nordic Bioscience A/S., Anne Sofie Siebuhr Employee of: Nordic Bioscience, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

THU0384 IMPACT OF IXEKIZUMAB ON WORK PRODUCTIVITY IN NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS PATIENTS: RESULTS FROM THE COAST-X TRIAL AT 52 WEEKS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 426-426
Author(s):  
A. Deodhar ◽  
P. J. Mease ◽  
L. S. Gensler ◽  
P. Rahman ◽  
V. Navarro-Compán ◽  
...  
Keyword(s):  
Axial Spondyloarthritis ◽  
Work Productivity ◽  
Analysis Of Covariance ◽  
Full Time ◽  
Research Support ◽  
Open Label ◽  
Activity Impairment ◽  
Work Activity ◽  
Work Impairment ◽  
Part Time

Background:Patients with non-radiographic axial spondyloarthritis (nr-axSpA) experience impairments in health-related quality of life comparable to those seen in ankylosing spondylitis, including impacts on work productivity. Ixekizumab (IXE) is a high-affinity monoclonal antibody that selectively targets interleukin-17A and effectively treats axial spondyloarthritis.1,2,3Objectives:This analysis evaluated the effect of IXE treatment for 52 weeks on work productivity and activity impairment as measured by absenteeism, presenteeism, overall work impairment, and activity impairment in patients with active nr-axSpA.Methods:COAST-X (NCT02757352) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group outpatient study investigating the efficacy and safety of 80 mg IXE every 2 weeks (Q2W) and every 4 weeks (Q4W) compared to placebo (PBO) in 303 patients naïve to biologic disease-modifying anti-rheumatic drugs with active nr-axSpA during a 52-week treatment period. From Weeks 16 through 44, if patients’ disease activity required escalation of treatment at investigator discretion, patients were switched to open-label IXE Q2W or subsequent tumor necrosis factor inhibitor treatment. Analysis was performed for the intent-to-treat population, which included data up to the time of biologic switching. Patients who switched to open-label IXE were considered non-responders. Changes from baseline in work productivity were measured for patients reporting full- or part-time work at Weeks 16 and 52 with the Work Productivity and Activity Impairment (WPAI) Questionnaire for Spondyloarthritis and analyzed with an analysis of covariance model including treatment, geographic region, screening magnetic resonance imaging and C-reactive protein level status, and baseline value as factors. Missing data was imputed using the modified baseline observation carried forward.Results:A majority of patients (63.5–65.7%) reported part-time or full-time paid work at baseline, with baseline scores for presenteeism and overall work activity slightly higher for patients in the PBO arm (p<0.05). Patients treated with IXE Q4W had significantly greater improvement than PBO in activity impairment at Weeks 16 (p=0.003) and 52 (p=0.004), presenteeism at Weeks 16 (p=0.007) and 52 (p=0.003), and overall work impairment at Weeks 16 (p=0.014) and 52 (p=0.005; Figure). Patients treated with IXE Q2W had significantly greater improvement than PBO in activity impairment at Weeks 16 (p=0.007) and 52 (p=0.006; Figure). Patients treated with either IXE regimen had numeric improvements in all WPAI measures compared to those receiving PBO at Weeks 16 and 52 (Figure).Conclusion:Patients with nr-axSpA treated with either IXE regimen had significant improvements in activity impairment compared to PBO. Patients receiving IXE Q4W also had significant improvements in presenteeism and overall work impairment.References:[1]Sieper, et al. (2016)Clin Exp Rheumatol.34(6):975-83.[2]Van der Heijde, et al. (2018)Lancet. 392(10163):2441-51.[3]Deodhar, et al. (2019)Arthritis Rheumatol.71(4):599-611.Figure.Changes from baseline in A) Absenteeism, B) Presenteeism, C) Overall Work Impairment, and D) Activity Impairment.Disclosure of Interests:Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, Lianne S. Gensler Grant/research support from: Pfizer, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, GSK, Novartis, UCB, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, Helena Marzo-Ortega Grant/research support from: Janssen, Novartis, Consultant of: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB, Theresa Hunter Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Baojin Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ann Leung: None declared, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB

FRI0277 EFFECTIVENESS OF BDMARDS IN AS AND NR-AXSPA PATIENT POPULATIONS: EXPERIENCE FROM THE CORRONA REGISTRY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 725.1-726
Author(s):  
T. Hunter ◽  
T. Blachley ◽  
W. Malatestinic ◽  
L. Harrold ◽  
B. Dube ◽  
...  
Keyword(s):  
Disease Activity ◽  
Patient Characteristics ◽  
Response Rates ◽  
Tender Joint Count ◽  
Research Support ◽  
Tender Joint ◽  
Clinical Registry ◽  
Modest Improvement ◽  
Asas Criteria ◽  
Patient Reported

Background:Axial spondyloarthritis (axSpA) consists of ankylosing spondylitis (AS), also referred to as radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). AxSpA can lead to reduced mobility, pain, fatigue, and impact quality of life. While bDMARDs are available for treatment, the literature lacks studies exploring their real-world effectiveness in clinical registry patients with axSpA.Table 1.Demographic characteristics and clinical response rates of AxSpA patientsTable 2.TNFi drug survival rate results of early and late disease courseObjectives:To describe patient characteristics of bDMARD initiators among the AS and nr-axSpA populations and the effectiveness of bDMARDs at the 6-month (± 3) post-initiation follow-up (FU) visit in the Corrona PsA/SpA Registry.Methods:This study included patients aged ≥ 18 years with AS per modified NY criteria and nr-axSpA per ASAS criteria enrolled between 3/2013 and 9/2019. Concurrently diagnosed patients with PsA were excluded. Baseline characteristics, such as demographic, clinical, disease activity, treatment, and patient-reported outcomes (PRO), were collected for those initiating a bDMARD at enrollment or during FU; response rates and mean change in disease activity and PRO between initiation and 6-month FU were calculated.Results:The AS (n=179) and nr-axSpA (n=32) bDMARD initiators groups were similar at initiation for mean age (AS: 49.1 yrs, nr-axSpA: 48.9 yrs), ASDAS scores (AS: 2.9, nr-axSpA: 2.8) and patient global assessment (AS: 59.6, nr-axSpA: 60.0). The two groups were different for time from disease duration (AS 8.5 yrs, nr-axSpA, 6.6 yrs), current NSAID use (AS: 64.2%, nr-axSpA: 46.9%) and naivete to cDMARDS (AS: 70.4%, nr-axSpA: 40.6%), TNFs (AS: 47.5%, nr-axSpA: 21.9%), non-TNFs (AS: 96.1%, nr-axSpA: 93.8%) and bDMARDs (AS: 46.9%, nr-axSpA: 21.9%). Patients were similarly impacted by their condition for BASDAI (AS: 5.0, nr-axSpA, 5.6), pain (AS: 55.8, nr-axSpA, 60.8) and fatigue (AS: 51.6, nr-axSpA, 59.9), but there was an imbalance in tender joint count (AS: 2.6, nr-axSpA, 13.4).At 6-month FU, both populations experienced minimal or no change in ASDAS scores (AS: -0.3, nr-axSpA: 0.0) remaining in a high state of disease activity (ASDAS, ≥2.2). A small percent of both groups achieved ASAS20 (AS: 20.1%; nr-axSpA: 21.9%) and ASAS40 (AS: 14 %, nr-axSpA: 15.6%). Further, bDMARD initiators had minimal decreases in BASDAI (AS: -0.6, nr-axSpA: -0.8), pain (AS: -8.5, nr-axSpA: -12.2), and fatigue (AS: -5.0, nr-axSpA: -7.9) scores.Conclusion:AS and nr-axSpA bDMARD initiators had a modest improvement in outcomes at six months. Twenty percent or fewer patients achieved ASAS20 or ASAS40, with many having residual impairment based on ASDAS, BASDAI, pain, and fatigue outcomes at six months. While patients are initiating biologic agents, room for improvement exists as many are not achieving optimal treatment response of inactive (ASDAS, <1.3) or low disease activity (ASDAS, <2.1).Disclosure of Interests:Theresa Hunter Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Taylor Blachley Employee of: Corrona, LLC, William Malatestinic Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Leslie Harrold Shareholder of: Corrona, LLC – shareholder, Grant/research support from: Pfizer – grant/research support, Consultant of: AbbVie, BMS, Roche – consultant, Employee of: Corrona, LLC – employment, Blessing Dube Employee of: Corrona, LLC, Meghan Glynn Shareholder of: Corrona, LLC – shareholder, Grant/research support from: Pfizer – grant/research support, Employee of: Corrona, LLC – employment, Jeffrey Lisse Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Rebecca Bolce Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

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