scholarly journals POS1020 EFFICACY OF TOFACITINIB ON DACTYLITIS IN INDIVIDUAL DIGITS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 777.2-778
Author(s):  
A. M. Orbai ◽  
P. J. Mease ◽  
P. Helliwell ◽  
O. Fitzgerald ◽  
M. Bdewi ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Research Support ◽  
Two Phase ◽  
Janus Kinase Inhibitor ◽  
Treatment Groups ◽  
Link Type ◽  
Hands And Feet ◽  
Post Hoc

Background:Dactylitis, a hallmark of psoriatic arthritis (PsA), is a uniformly diffuse and sometimes painful swelling of the fingers and/or toes.1 Up to 50% of patients (pts) with PsA may experience dactylitis;1,2 as such, dactylitis is an accepted domain of PsA that should be considered in treatment decisions.3 In PsA, dactylitis typically involves feet more than hands; dactylitic joints more frequently have erosive damage, compared with non-dactylitic joints.2 There remains a need for effective therapies to treat dactylitis in pts with PsA. Improvements in dactylitis have been associated with tofacitinib, an oral Janus kinase inhibitor for the treatment of PsA.4,5Objectives:To assess the effect of tofacitinib on dactylitis by location (hands/feet) and individual digit involvement in pts with PsA.Methods:These post hoc analyses used data pooled from two Phase 3 studies (12-month OPAL Broaden [NCT01877668];5 6-month OPAL Beyond [NCT01882439]4) in pts with active PsA treated with tofacitinib 5 mg twice daily (BID; approved dose; to Month [M] 6), tofacitinib 10 mg BID (to M6) or placebo (PBO; to M3); pts were treated continuously with a single conventional synthetic disease-modifying antirheumatic drug. Pts were categorised by the presence of dactylitis at baseline (BL) in the hands and/or feet. Endpoints included change from BL in Dactylitis Severity Score (DSS),6 the number of dactylitic digits and the proportion of pts with dactylitis in individual digits at M1, M3 and M6. Descriptive statistics were generated by visit and treatment arm.Results:Data were pooled from 373 pts with DSS >0 at BL. BL characteristics, including gender, age, race, body mass index, PsA duration, BL DSS and dactylitic digits count were similar across dactylitis groups and treatment groups, except for pts with dactylitis in both the hands and feet, who had higher DSS compared to those with dactylitis in the hands or feet only, likely due to having more dactylitic digits (data not shown). Regardless of location, pts treated with tofacitinib had cumulative improvements from BL to M6 in DSS (Figure 1a) and in the number of dactylitic digits (Figure 1b); improvements in DSS were greater at M1 and M3, compared with PBO. Pts treated with tofacitinib 10 mg BID typically had numerically greater improvements in DSS, compared with pts treated with tofacitinib 5 mg BID (Figure 1a). Most pts treated with tofacitinib experienced improvement of dactylitis across all fingers and toes (Figure 1c–f); mean dactylitis presence was ≤15% at M6 in pts treated with tofacitinib for all digits. Generally, at M1 and M3, fewer pts treated with tofacitinib had dactylitis in any digit, compared with PBO (Figure 1c–f).Conclusion:Among pts with pre-existing dactylitis, treatment with tofacitinib resulted in improvements in dactylitis in hands, feet, or both, and in all digits as early as M1, and up to M6.References:[1]Kaeley et al. Semin Arthritis Rheum 2018; 48: 263-273.[2]Brockbank et al. Ann Rheum Dis 2005; 64: 188-190.[3]Coates et al. Arthritis Rheumatol 2016; 68: 1060-1071.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.[5]Mease et al. N Engl J Med 2017; 377: 1537-1550.[6]Helliwell et al. J Rheumatol 2005; 32: 1745-1750.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Ana-Maria Orbai Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Horizon, Janssen, Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Oliver FitzGerald Speakers bureau: AbbVie, Janssen, Pfizer Inc, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Pfizer Inc, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis and Pfizer Inc, Mohammed Bdewi Speakers bureau: AbbVie, Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

SAT0139 AGE-BASED (<65 VS ≥65 YEARS) INCIDENCE OF INFECTIONS AND SERIOUS INFECTIONS IN TOFACITINIB-, ADALIMUMAB- AND PLACEBO-TREATED PATIENTS WITH RHEUMATOID ARTHRITIS: A POST HOC ANALYSIS OF PHASE 2, PHASE 3 AND PHASE 3B/4 TOFACITINIB STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1007-1008
Author(s):  
K. Winthrop ◽  
D. Gold ◽  
D. Henrohn ◽  
L. Wang ◽  
A. Shapiro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Active Treatment ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Research Support ◽  
Treatment Groups ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Post Hoc

Background:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). A recent ad hoc safety analysis (as of August 2019; may be subject to change) from an ongoing, open-label, randomised, post-authorisation safety study, Study A3921133 (NCT02092467), conducted in RA patients (pts) aged ≥50 years with ≥1 cardiovascular risk factor has shown that incidence rates (IRs) of serious infection events (SIEs) were higher with tofacitinib 10 mg BID vs tumour necrosis factor inhibitors (TNFi; adalimumab [ADA] and etanercept) and this difference was more pronounced in pts aged ≥65 years (Pfizer Inc; data on file).Objectives:To assess the IRs of overall infection events and SIEs in pts from Phase (P)2, P3 and P3b/4 tofacitinib RA trials which had a TNFi (ADA) active control or comparator arm.Methods:This is a post hoc analysis of Month 0–12 data pooled from P2 (A3921035;NCT00550446[first 12-week randomised parallel treatment period only]), P3 (ORAL Standard;NCT00853385) and P3b/4 (ORAL Strategy;NCT02187055) studies. Pts randomised to receive tofacitinib 5 mg BID, tofacitinib 10 mg BID, ADA 40 mg subcutaneously every other week and placebo (PBO) were included and assessed overall and by age (<65 or ≥65 years). SIEs were defined as infections requiring hospitalisation or parenteral antimicrobial therapy, or meeting other criteria for a serious adverse event. IRs (pts with events/100 pt-years of exposure [PY]) and 95% confidence intervals (CIs) were calculated for all infection events and SIEs; only the first infection events that occurred up to 28 days after the last dose or to the data cut-off date were considered.Results:Of 2180 pts included in the pooled studies (tofacitinib 5 mg BID: N=1064 [943.4 PY]; tofacitinib 10 mg BID: N=306 [236.6 PY]; ADA: N=643 [554.3 PY]; PBO: N=167 [108.1 PY]), 1841 (84.4%) were aged <65 years and 339 (15.6%) were aged ≥65 years. In general, the IRs for all infection events and SIEs were higher with tofacitinib 5 mg BID, tofacitinib 10 mg BID and ADA in pts aged ≥65 years compared with pts aged <65 years. Overall and when stratified by age, IRs for all infection events were similar across the active treatment groups (Figure 1); IRs with PBO were lower vs the active treatment groups overall and in pts aged <65 years, and numerically lower vs the active treatment groups in pts aged ≥65 years. IRs for SIEs were comparable across active treatment groups in pts aged <65 years, while among pts aged ≥65 years, IRs were numerically higher for tofacitinib 10 mg BID vs ADA, and appeared to be similar for tofacitinib 5 mg BID and ADA (Figure 2).Conclusion:In this analysis of data pooled from P2, P3 and P3b/4 tofacitinib RA studies which included a TNFi arm (ADA), the risk of SIEs or infections overall was similar for tofacitinib and ADA with the exception of a numerically higher rate of SIEs with tofacitinib 10 mg BID vs ADA in pts aged ≥65 years. In most countries, tofacitinib 10 mg BID is not an approved dose for the treatment of RA. This post hoc comparison is limited by variation in sample size and PY of exposure between treatment and age groups, and a small number of cases of SIEs in the ≥65-year age group resulting in wide 95% CIs; interpretation of results should be made with caution. The findings in the present analysis are consistent with increasing age being a known risk factor for infections.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Christina Viegelmann of CMC Connect and funded by Pfizer Inc.Disclosure of Interests: :Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, David Gold Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dan Henrohn Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Hendrik Schulze-Koops Grant/research support from: Pfizer Inc

scholarly journals AB0774 TIME TO RESPONSE FOR CLINICAL AND PATIENT-REPORTED OUTCOMES IN PATIENTS WITH PSORIATIC ARTHRITIS TREATED WITH TOFACITINIB, ADALIMUMAB OR PLACEBO

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1685.2-1685
Author(s):  
D. D. Gladman ◽  
L. C. Coates ◽  
J. Wu ◽  
L. Fallon ◽  
M. A. Hsu ◽  
...  
Keyword(s):  
Disease Activity ◽  
Kinase Inhibitor ◽  
Initial Response ◽  
Analysis Data ◽  
Janus Kinase ◽  
Research Support ◽  
Two Phase ◽  
Treatment Groups ◽  
Link Type ◽  
Patient Reported

Background:With multiple disease domains affected in PsA, clinical and patient-reported outcome (PRO) measures are important to assess disease improvement following treatment. Rapid, meaningful improvements in disease activity are a priority for physicians and patients (pts). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Higher proportions of pts achieved responses in PROs and clinical measures when treated with tofacitinib for 3 months vs placebo (PBO).1-5Proportions of responders were also similar between tofacitinib and adalimumab (ADA) after 3, 6 and 12 months.2,3,5Objectives:To determine the time to initial response using responder definitions for selected PROs and clinical endpoints in pts with active PsA treated with tofacitinib, ADA or PBO switching to tofacitinib.Methods:In this post hoc analysis, data were collected from two Phase 3 studies (OPAL Broaden [12 months;NCT01877668]; OPAL Beyond [6 months;NCT01882439]).3,4Pts receiving tofacitinib 5 or 10 mg twice daily (BID), subcutaneous ADA 40 mg once every two weeks (Q2W; OPAL Broaden only), or PBO switching to tofacitinib 5 or 10 mg BID at Month (M)3, were included. Responder definitions included: HAQ-DI ≥0.35-point improvement from baseline (BL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score ≥4-point improvement from BL, minimal disease activity (MDA) yes/no composite response (meeting at least 5 of 7 criteria) and PsA Disease Activity Score (PASDAS) post-BL score of ≤3.2 and >1.6-point improvement from BL. First post-BL data were collected at Week 2 (eg for HAQ-DI) or M1. Time-to-event analyses were performed using the Kaplan-Meier (KM) method, with pts censored at the last observed visit. Log-rank tests compared time to initial response across treatment groups.Results:KM analyses show days to initial response (Figure 1, Figure 2). Time to initial HAQ-DI response was significantly different between treatment groups in OPAL Broaden (p<0.01): faster response in pts receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID and ADA 40 mg Q2W vs pts who switched from PBO to tofacitinib at M3 (Figure 1a). A similar, but not significant (ns), trend was observed for HAQ-DI responses in OPAL Beyond (Figure 1b). Generally, initial FACIT-F responses were achieved faster (ns) in pts receiving tofacitinib 5 mg BID vs other treatment in both studies (Figure 1c, Figure 1d). Times to initial MDA and PASDAS responses were similar between tofacitinib and ADA treatment groups (Figure 2).Conclusion:Times to initial response in functional ability and disease activity were similar in pts treated with either tofacitinib or ADA. Time to initial response prior to first post-BL observation (Week 2 or M1) was not estimable in this analysis. These results may help physicians better understand the time frame for a meaningful response in pts receiving tofacitinib.References:[1]Strand et al. RMD Open 2019;5:e000808.[2]Strand et al. RMD Open 2019;5:e000806.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.[5]Helliwell et al. Arthritis Res Ther 2018;20:242.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Laura C Coates: None declared, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Elizabeth Bacci Employee of: Evidera, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip Helliwell: None declared

scholarly journals POS1025 TOFACITINIB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS AND PROBABLE DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF TWO PHASE 3 CLINICAL TRIALS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 782.1-782
Author(s):  
L. Gossec ◽  
G. Citera ◽  
A. Sellas-Fernández ◽  
D. C. Gruben ◽  
M. Valderrama ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Research Support ◽  
Phase 3 ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Sf 36 ◽  
Global Pain ◽  
Post Hoc

Background:Depression and anxiety are highly prevalent in patients (pts) with psoriatic arthritis (PsA),1 with inflammation a key pathogenic feature of depression in these pts.2 Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. It acts by modulating immune and inflammatory responses. The link between major depressive disorder/generalised anxiety disorder (MDD/GAD), inflammation and tofacitinib effectiveness has not been fully explored.Objectives:Analyse the prevalence of probable MDD/GAD in pts with PsA initiating tofacitinib treatment and the impact of baseline (BL) probable MDD/GAD status on tofacitinib efficacy in these pts.Methods:This was a post hoc analysis of data from pts who received tofacitinib 5 or 10 mg twice daily (BID), or placebo (PBO), pooled from two Phase 3 trials (12-month OPAL Broaden [NCT01877668];3 6-month OPAL Beyond [NCT01882439]4). Pts with BL probable MDD and/or GAD were identified by a Short Form-36 Health Survey (SF-36) Mental Component Summary score (MCS) ≤38. Pt demographics/BL characteristics and outcomes were stratified by the presence (SF-36 MCS ≤38) or absence (SF-36 MCS >38) of BL probable MDD/GAD. At Months (M)3/6/9/12, changes from BL in SF-36 MCS were evaluated, and efficacy assessed by the proportions of pts who achieved: Psoriatic Arthritis Disease Activity Score (PASDAS) ≤3.2, Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement ≥0.35 and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) improvement ≥4. BL global pain was measured via visual analogue scale.Results:Of the 706 pts included in this analysis, BL probable MDD/GAD was identified in 46.2%, 44.9% and 46.2% of pts in the tofacitinib 5 mg BID (108/234), tofacitinib 10 mg BID (106/236) and PBO (109/236) groups, respectively. BL disease activity was similar across the three treatment groups, independent of probable MDD/GAD status (mean PASDAS: 6.1–6.4 in pts with vs 5.8–6.1 in pts without probable MDD/GAD). In the tofacitinib 5 mg BID group, mean BL scores for HAQ-DI (1.4 vs 1.0), FACIT-F total score (20.5 vs 32.4) and global pain (61.3 vs 51.5) indicated worse disability, fatigue and pain, respectively, for pts with vs without BL probable MDD/GAD. Similar findings were seen in the tofacitinib 10 mg BID and PBO groups. At M3, improvements from BL in SF-36 MCS in pts with probable MDD/GAD were numerically, but not significantly, greater with tofacitinib 5 and 10 mg BID vs PBO, and these changes were largely sustained to M12 (Figure 1a). At M3, numerically greater proportions of pts achieved improvements in PASDAS, HAQ-DI and FACIT-F with tofacitinib 5 or 10 mg BID vs PBO, regardless of BL probable MDD/GAD status (Figure 1b–d). Through M3–12, the proportions of pts who achieved PASDAS ≤3.2 with tofacitinib 5 or 10 mg BID were generally significantly greater in pts without vs with probable MDD/GAD (Figure 1b). At all timepoints, rates of improvement in HAQ-DI with tofacitinib 5 mg BID were numerically greater in pts with vs without probable MDD/GAD, whereas the opposite was true for tofacitinib 10 mg BID (Figure 1c). FACIT-F improvement rates with tofacitinib 10 mg BID were consistently numerically greater in pts with vs without probable MDD/GAD, while findings were mixed for tofacitinib 5 mg BID (Figure 1d).Conclusion:Around 46% of pts with PsA treated with tofacitinib had BL probable MDD/GAD (SF-36 MCS ≤38). Pts with BL probable MDD/GAD treated with tofacitinib had sustained changes in SF-36 MCS. Rates of clinical improvement with tofacitinib were generally greater in pts without vs with probable MDD/GAD, whereas findings for disability and fatigue improvements varied between tofacitinib doses. Further research is required to evaluate the relationship between PsA and depression, to improve treatment targets and the quality of life of pts with PsA.References:[1]Zhao et al. Clin Rheumatol 2020; 39: 217-225.[2]Mathew & Chandran. Rheumatol Ther 2020; 7: 287-300.[3]Mease et al. N Engl J Med 2017; 377: 1537-1550.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Deeks, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Laure Gossec Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Roche, UCB, Gustavo Citera Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Agustí Sellas-Fernández: None declared, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Monica Valderrama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Susana Gómez Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

scholarly journals AB0831 COMPARISON OF DIFFERENT REMISSION INDICES IN PATIENTS WITH PSORIATIC ARTHRITIS: A POST HOC ANALYSIS OF DATA FROM PHASE 3 TOFACITINIB STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1720-1721
Author(s):  
E. Schneeberger ◽  
G. Citera ◽  
P. Nash ◽  
J. S. Smolen ◽  
P. J. Mease ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Janus Kinase ◽  
Research Support ◽  
Phase 3 ◽  
Low Disease Activity ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Moderate Agreement ◽  
Post Hoc

Background:An international task force has agreed that remission and low disease activity (LDA) are treatment targets for patients (pts) with PsA, and recommends the Disease Activity Index in Psoriatic Arthritis (DAPSA) and minimal disease activity (MDA) to assess disease activity states.1Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:In this post hoc analysis, we compared DAPSA LDA with MDA, and DAPSA remission with very low disease activity (VLDA) and DAS28-3(CRP) remission, in pts with PsA receiving tofacitinib.Methods:Data were pooled from 2 Phase 3 studies (OPAL Broaden [12 months;NCT01877668]; OPAL Beyond [6 months;NCT01882439]) for pts receiving tofacitinib 5 or 10 mg twice daily (BID) or placebo (PBO). DAPSA was determined by summing: swollen joint count (SJC66); tender/painful joint count (TJC68); Patient’s Global Assessment of Arthritis (PtGA; visual analogue scale [VAS]); pain (VAS); and CRP. Pts were classified as achieving MDA or VLDA when meeting ≥5 (MDA) or 7 (VLDA) of the following criteria: TJC68 ≤1; SJC66 ≤1; Psoriasis Activity and Severity Index ≤1 or body surface area ≤3%; pain (VAS) ≤15; PtGA (VAS) ≤20; HAQ-DI ≤0.5; tender entheseal points (using Leeds Enthesitis Index [LEI]) ≤1. A logistic regression model was used to assess demographic and baseline characteristics as predictors of a trend in DAPSA scores at Month (M)3. DAPSA LDA (≤14), MDA, DAPSA remission (DAPSA ≤4), VLDA and DAS28-3(CRP) remission (DAS28-3[CRP]<2.6) rates were compared at M1, M3 and M6 for pts receiving tofacitinib 5 mg BID and at M6 for pts receiving tofacitinib 5 or 10 mg BID. Agreement between disease activity indices at M6 was evaluated using a kappa test. The percentage of tofacitinib-treated pts who achieved MDA, VLDA and non-response was reported at M6, stratified by achievement of DAPSA LDA, remission or non-response.Results:This analysis included 709 pts: tofacitinib 5 mg BID, n=237; tofacitinib 10 mg BID, n=236; PBO, n=236. At M3, older patients treated with tofacitinib, and tofacitinib- or PBO-treated pts with higher baseline SJC66, TJC68, PtGA VAS, HAQ-DI, LEI and Pain VAS, were significantly (p<0.05) more likely to have higher DAPSA. DAPSA LDA, MDA, remission (DAPSA and DAS28-3[CRP]) and VLDA rates generally increased from M1 to M6 for patients receiving tofacitinib 5 mg BID (Figure a). At M6, most tofacitinib-treated pts who achieved MDA, and all who achieved VLDA, were also in DAPSA remission or LDA (Figure b). At least moderate agreement (defined by kappa values 0.41–0.60) was observed between DAPSA LDA and MDA, and between DAPSA remission and VLDA, with both doses of tofacitinib at M6 (Figure c).Conclusion:Remission and LDA rates generally increased over time in pts with PsA receiving tofacitinib. DAPSA LDA showed moderate agreement with MDA, and DAPSA remission showed at least moderate agreement with VLDA, confirming that DAPSA and MDA are useful measurement tools to assess disease activity in pts with PsA treated with tofacitinib.References:[1]Smolen et al. Ann Rheum Dis 2018;77:3-17.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect, McCann Health Medical Communications, and funded by Pfizer Inc.Disclosure of Interests:Emilce Schneeberger: None declared, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, 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, 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, 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, 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, Claudia Helling Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette E Szumski Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Daniela Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dario Ponce de Leon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

scholarly journals POS1038 THE EFFECT OF FILGOTINIB ON ENTHESITIS: 100-WEEK DATA FROM AN OPEN-LABEL EXTENSION STUDY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 792.2-793
Author(s):  
P. Helliwell ◽  
L. C. Coates ◽  
F. Van den Bosch ◽  
D. D. Gladman ◽  
L. Gheyle ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Treatment Effect ◽  
Janus Kinase ◽  
Research Support ◽  
Rapid Improvement ◽  
Open Label ◽  
Lateral Epicondyle ◽  
Link Type ◽  
Open Label Extension ◽  
Discriminatory Capacity

Background:Filgotinib (FIL), a novel preferential Janus kinase 1 inhibitor, was assessed in patients with active psoriatic arthritis (PsA) in the 16-week, Phase 2, EQUATOR trial (NCT03101670).1 EQUATOR2 (NCT03320876) is the open-label extension (OLE). As previously reported, an interim analysis of the OLE showed that the majority of patients had clinical resolution of enthesitis by Week 52.2Objectives:This post-hoc analysis evaluated the effect of FIL on clinical enthesitis after 100 weeks of treatment in the OLE, as assessed using the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, and evaluated the discriminatory capacity of the two indices. In addition, we assessed which of the sites included in LEI and SPARCC were most frequently involved and whether treatment effect was consistent across sites.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or placebo (PBO) once daily (QD) for 16 weeks. At Week 16, all patients could continue into the OLE, receiving FIL 200 mg QD for up to an additional 304 weeks. We compared changes from core baseline in LEI and SPARCC measures, the effect on enthesitis at sites included in LEI and SPARCC assessments and the discriminatory capacity of both enthesitis indices.Results:Of 131 patients randomised to EQUATOR, 122 entered the OLE. There was strong agreement between LEI and SPARCC at baseline. While most patients had enthesitis at baseline according to either index (76/131 [58.0%] by LEI; 85/131 [64.9%] by SPARCC), a minority had enthesitis at a large number of sites (6.9% with 5–6 LEI sites; 12.2% with ≥9 SPARCC sites). The sites most frequently involved at baseline were the lateral epicondyle humerus and Achilles tendon, sites common to both LEI and SPARCC. There was greater variability in the change from baseline to Week 16 in SPARCC compared with LEI (Table 1). LEI showed a greater discriminatory capacity than SPARCC when change from baseline was compared for FIL vs PBO at Week 16, as shown by higher absolute standardised mean difference: −0.70 (LEI) and −0.30 (SPARCC) (observed cases; Table 1). Subgroup analyses indicated that the treatment effect of FIL vs PBO at Week 16 for all sites was consistent with the overall treatment effect seen for LEI or SPARCC, and indicative of an improvement with FIL vs PBO for nearly all sites. The proportion of patients with enthesitis decreased from baseline up to OLE Week 100 (Figure 1). There were no major differences in long-term effect on enthesitis between sites.Conclusion:FIL improved enthesitis consistently across sites compared with PBO. Rapid improvement in enthesitis was seen up to Week 16 of the core study and improvements continued up to Week 52, after which responses were generally stable up to Week 100. LEI assesses fewer locations than SPARCC, but reassuringly captured the sites most commonly affected by enthesitis; LEI also had greater discriminatory capacity.References:[1]Mease P, et al. Lancet 2018;392:2367–77[2]Mease P, et al. Arthritis Rheumatol 2020;72(suppl 10): abstract 0910Figure 1.Acknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Eline Vetters, Leen Gilles, Benjamin Pett and his team, all employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of Interests:Philip Helliwell Speakers bureau: Janssen, Novartis, Paid instructor for: Pfizer, Consultant of: Eli Lilly, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Merck and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB.

scholarly journals Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura C. Coates ◽  
Johan K. Wallman ◽  
Dennis McGonagle ◽  
Georg A. Schett ◽  
Iain B. McInnes ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Pooled Analysis ◽  
Search Query ◽  
Two Phase ◽  
Pooled Data ◽  
Link Type ◽  
Full Resolution ◽  
Shift Analysis ◽  
Post Hoc ◽  
Future 2

Abstract Background Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. Method Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3–6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. Results A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3–6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. Conclusion Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. Trial registration FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013)

scholarly journals Evaluation of Ruxolitinib versus Best Available Therapy in Treating Primary Myelofibrosis

2021 ◽  
Author(s):  
Kawa M. Hasan ◽  
Ahmed Y. Elmeshhadany ◽  
Nazar P. Shabila
Keyword(s):  
Overall Survival ◽  
Kinase Inhibitor ◽  
Laboratory Data ◽  
Primary Myelofibrosis ◽  
Risk Groups ◽  
Janus Kinase ◽  
Response To Treatment ◽  
International Prognostic Scoring System ◽  
Janus Kinase Inhibitor ◽  
Treatment Groups

Objectives: Ruxolitinib is a Janus kinase inhibitor (JAK) that is approved for the treatment of myelofibrosis. The therapeutic protocol has changed after the introduction of Ruxolitinib. The aim of this study was to evaluate the effectiveness of Ruxolitinib and to compare it with best available therapy in patients with primary myelofibrosis. Methods: In this retrospective study, 72 patients with primary myelofibrosis were scrutinized in the period from 2012 to 2018 at Nanakali hemato-oncology teaching center, Erbil, Iraqi Kurdistan. The patients were divided into 2 cohorts, 26 of them were treated with Ruxolitinib and 46 others received best available therapy. The patients’ characteristics, their response to treatment, and the outcomes were evaluated. The efficacy of treatment in both arms was compared. Results: The majority our studied patients (46, 63.8%) were in the high and intermediate-2 risk groups according to international prognostic scoring system. At time of diagnosis, there were no noticeable differences in the clinical characteristics and laboratory data among the Ruxolitinib and best available treatment groups of patients. Ruxolitinib was found to be effective in reducing the size of spleen and improving the overall survival when compared to best available treatment group (p<0.001, p= 0.008 respectively). The patients’ performance state had a significant effect on the overall survival in both treatment groups (p=0.003). Conclusion: Ruxolitinib has a significant role in reduction of spleen size, and potentially affect the survival outcomes in patients with myelofibrosis. Keywords: Ruxolitinib, Myelofibrosis, Splenomegaly, Outcomes.

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