scholarly journals AB0259 EVALUATION OF THE EFFECT OF FILGOTINIB ON THE PHARMACOKINETICS OF ROSUVASTATIN, ATORVASTATIN, AND PRAVASTATIN

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1155.3-1156
Author(s):  
K. Anderson ◽  
C. Nelson ◽  
Q. Gong ◽  
M. Alani ◽  
T. Tarnowski ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Dose ◽  
Organic Anion ◽  
Janus Kinase ◽  
Lipid Lowering ◽  
Pharmacokinetic Parameters ◽  
Inadequate Response ◽  
Post Hoc Analysis ◽  
Cardiovascular Morbidity And Mortality ◽  
Post Hoc

Background:Filgotinib is an orally administered small molecule that preferentially inhibits Janus kinase 1 and is approved for use in Europe and Japan in adult patients with rheumatoid arthritis (RA) who have had an inadequate response to conventional therapies. Patients with RA are at a higher risk of cardiovascular morbidity and mortality relative to the general population1. Thus, it is important to understand potential drug-drug interactions of filgotinib with lipid-lowering agents such as statins. Based on in vitro studies, filgotinib is not expected to significantly increase exposure of statins via inhibition of the organic anion transporting peptide (OATP) at clinically relevant exposures. Hence, in Phase 2 and Phase 3 clinical studies, statins were allowed for use with filgotinib. A post-hoc analysis showed no increase in statin-induced AEs such as muscle or liver toxicities when statins were coadministered with filgotinib (“Concomitant Use of Statins in Filgotinib-Treated Patients with Rheumatoid Arthritis: A Post Hoc Analysis”, submitted to EULAR 2021).Objectives:The objectives of this study (NCT04608344) were to evaluate the effect of filgotinib on the pharmacokinetics of atorvastatin, pravastatin, and rosuvastatin, which are sensitive substrates for the OATP-1B1/1B3, and the short-term safety of administering filgotinib with or without statins.Methods:This was an open-label, randomized, two-way, crossover study in healthy adult volunteers (n = 27). Study participants received a single dose of atorvastatin (ATV 40 mg) and a single dose of a cocktail of pravastatin (PRA 40 mg)/rosuvastatin (ROS 10 mg), on two different occasions with washout in between, alone or in combination with filgotinib (200 mg QD for 11 days). Serial pharmacokinetic sampling was performed and pharmacokinetic parameters for each statin were calculated. Safety was assessed throughout the study. An analysis of variance using a mixed-effects model was applied to the natural logarithmic transformation of pharmacokinetic parameters (Cmax and AUCinf) for ATV, 2-OH-ATV (active metabolite of ATV), PRA, and ROS. Geometric-least squares means (GLSM) ratios and 90% confidence intervals (90% CI) of pharmacokinetic parameters were estimated for each analyte and were compared against pre-specified lack of pharmacokinetic alteration boundaries of 70 to 143%.Results:Of the 27 enrolled participants, 25 participants completed all study treatments. Most AEs and laboratory abnormalities were Grade 1 or 2 in severity; 1 participant discontinued due to a Grade 3 increase in creatine kinase and 1 participant discontinued due to difficulty in blood draws. Following coadministration of filgotinib with ATV, relative to ATV alone, ATV AUCinf was unaffected (GLSM ratio (90% CI): 0.91 (0.84, 0.99)), but ATV Cmax was slightly reduced (GLSM ratio (90% CI): 0.82 (0.69, 0.98)). 2-OH-ATV exposure (Cmax and AUCinf) were unaffected (GLSM ratio (90% CI): 0.98 (0.81, 1.18) for Cmax and 1.12 (1.02, 1.22) for AUCinf), and were within the pre-specified lack-of-effect bounds. Following coadministration with filgotinib, PRA AUCinf was unaffected (GLSM ratio (90% CI): 1.22 (1.06, 1.42)), but PRA Cmax was slightly higher (1.25 (1.01, 1.54)). ROS exposure (Cmax and AUCinf) were moderately higher upon coadministration with filgotinib (GLSM ratio (90% CI): 1.68 (1.43, 1.97) for Cmax and 1.42 (1.30, 1.56) for AUCinf), and these changes in rosuvastatin exposure are not considered to be clinically relevant.Conclusion:All study treatments were generally well tolerated. Co-administration with filgotinib did not have a clinically meaningful impact on the exposure of ATV, PRA, and ROS. These data support concomitant use of filgotinib with OATP substrates such as statins.References:[1]Piepoli MF, Hoes AW, Agewall S, et al. Eur Heart J. 2016;37(29): 2315-2381.Disclosure of Interests:Kacey Anderson Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Cara Nelson Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Qi Gong Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Thomas Tarnowski Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Ahmed A. Othman Shareholder of: Gilead Sciences, Employee of: Gilead Sciences

scholarly journals Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Vibeke Strand ◽  
Jeffrey Kaine ◽  
Rieke Alten ◽  
Gene Wallenstein ◽  
Annette Diehl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Physical Function ◽  
Global Assessment ◽  
Janus Kinase ◽  
Patient Global Assessment ◽  
Normative Values ◽  
Post Hoc Analysis ◽  
Patient Reported ◽  
Post Hoc

Abstract Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson’s Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients. Results Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients. Conclusions This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients’ perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care. Trial registration Clinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009)

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 Differences and similarities in clinical and functional responses among patients receiving tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate: a post hoc analysis of data from ORAL Strategy

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Roy Fleischmann ◽  
Noriko Iikuni ◽  
Harry Shi ◽  
Koshika Soma ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Activity Index ◽  
Cumulative Probability ◽  
Inadequate Response ◽  
Combination Therapies ◽  
Functional Responses ◽  
Strategy Study ◽  
Post Hoc Analysis ◽  
Probability Plots ◽  
Post Hoc

Abstract Background This post hoc analysis assessed clinical and functional responses to tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab + MTX, in patients with rheumatoid arthritis enrolled in the ORAL Strategy study, including evaluation of patient-level data using cumulative probability plots. Methods In the 12-month, phase IIIb/IV ORAL Strategy study, patients with rheumatoid arthritis and an inadequate response to MTX were randomized to receive tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID + MTX, or adalimumab 40 mg every other week + MTX. In this post hoc analysis, cumulative probability plots were generated for mean percent change from baseline (%∆) in the Clinical Disease Activity Index (CDAI; clinical response) and mean change from baseline (∆) in the Health Assessment Questionnaire-Disability Index (HAQ-DI; functional response) at month 12. Median C-reactive protein (CRP) levels by time period were summarized by CDAI remission (≤ 2.8) status at months 6 and 12. Results Data for 1146 patients were analyzed. At month 12, cumulative probability plots for %∆CDAI and ∆HAQ-DI were similar across treatments in patients with greater response. At lower levels of response, patients receiving tofacitinib monotherapy did not respond as well as those receiving combination therapies. With tofacitinib + MTX, numerically higher baseline CRP levels and numerically larger post-baseline CRP reductions were seen in patients achieving CDAI remission at months 6 and 12 vs those who did not. Conclusions These results suggest that patients with a greater response did well, irrespective of which therapy they received. Patients with lesser response had better outcomes with combination therapies vs tofacitinib monotherapy, suggesting they benefitted from MTX. High pre-treatment CRP levels may be associated with better response to tofacitinib + MTX. Trial registration ClinicalTrials.gov, NCT02187055. Registered on 08 July 2014.

Differences and Similarities in Clinical and Functional Responses Among Patients Receiving Tofacitinib Monotherapy, Tofacitinib Plus Methotrexate, and Adalimumab Plus Methotrexate: A Post-hoc Analysis of Data From Oral Strategy

2021 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Roy Fleischmann ◽  
Noriko Iikuni ◽  
Harry Shi ◽  
Koshika Soma ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Activity Index ◽  
Cumulative Probability ◽  
Inadequate Response ◽  
Combination Therapies ◽  
Functional Responses ◽  
Strategy Study ◽  
Post Hoc Analysis ◽  
Probability Plots ◽  
Post Hoc

Abstract BackgroundThis post-hoc analysis assessed clinical and functional responses to tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab + MTX, in patients with rheumatoid arthritis enrolled in the ORAL Strategy study, including evaluation of patient-level data using cumulative probability plots.MethodsIn the 12-month, phase IIIb/IV ORAL Strategy study, patients with rheumatoid arthritis and an inadequate response to MTX were randomized to receive tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID + MTX, or adalimumab 40 mg every other week + MTX. In this post-hoc analysis, cumulative probability plots were generated for mean percent change from baseline (%∆) in Clinical Disease Activity Index (CDAI; clinical response) and mean change from baseline (∆) in Health Assessment Questionnaire-Disability Index (HAQ-DI; functional response) at month 12. Median C-reactive protein (CRP) levels by time period were summarized by CDAI remission (≤2.8) status at months 6 and 12. ResultsData for 1146 patients were analyzed. At month 12, cumulative probability plots for %∆CDAI and ∆HAQ-DI were similar across treatments in patients with greater response. At lower levels of response, patients receiving tofacitinib monotherapy did not respond as well as those receiving combination therapies. With tofacitinib + MTX, numerically higher baseline CRP levels and numerically larger post-baseline CRP reductions were seen in patients achieving CDAI remission at months 6 and 12 vs those who did not.ConclusionsThese results suggest that patients with a greater response did well, irrespective of which therapy they received. Patients with lesser response had better outcomes with combination therapies vs tofacitinib monotherapy, suggesting they benefitted from MTX. High pre‑treatment CRP levels may be associated with better response to tofacitinib + MTX. Trial registrationClinicalTrials.gov, NCT02187055. Registered 08 July 2014, https://clinicaltrials.gov/ct2/show/NCT02187055?term=NCT02187055&draw=2&rank=1

High disease activity is associated with higher blood pressure in recent onset rheumatoid arthritis patients, post-hoc analyses of IMPROVED study

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Gegenava ◽  
SA Bergstra ◽  
H Maassen ◽  
CF Allaart
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Pressure ◽  
Disease Activity ◽  
Classification Criteria ◽  
Recent Onset ◽  
American College Of Rheumatology ◽  
Cardiovascular Morbidity And Mortality ◽  
The Difference ◽  
Post Hoc ◽  
Acpa Status

Abstract Funding Acknowledgements Type of funding sources: None. Background Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high prevalence of cardiovascular morbidity and mortality. Purpose: purpose of our project was to investigate the association between disease activity and systolic and diastolic blood pressure (SBP, DBP) in patients with recent-onset rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) who were treated to target disease activity score (DAS)&lt;1.6 in the IMPROVED study. Methods: The associations between disease activity and SBP/DBP were tested for 610 patients (364 RA, 246 UA), cross-sectionally and over time. GEE analyses were performed with both SBP and DBP as outcome measures and disease activity categories (DAS&lt;1.6;&gt;1.6 but ≤2.4; &gt;2.4), CRP level, treatment arms or the number of visits on a certain drug as potential predictors in separate analyses. Separate analyses tested potential contributions of gender, anti-cyclic citrullinated peptide antibodies (ACPA) status, and fulfilling the 2010 ACR/EULAR (American college of rheumatology/ European league against rheumatism) classification criteria. In addition association of BP with various levels of disease activity was tested with T-test. Results: At the baseline mean (SD) SBP was 133 (20) and DBP mean (SD) was 80 (10).  SBP &gt; 140mm Hg was observed in 40% of patients and DBP &gt; 90 mm Hg  in 21% of patients. SBP and DBP statistically significantly decreased during 5 years follow up (mainly during year 1), but the difference in mm Hg was small. Estimates from GEE analysis showed that patients with high DAS &gt;2.4 (HDAS) had a statistically significantly higher SBP (average 3 mm Hg higher, 95% CI 1.7; 4.2, p &lt; 0.01), than the patients in with DAS ≤2.4. ANOVA analyses showed a statistically significant association between SBP and DAS. In addition, post hoc analyses showed that patients with HDAS had a statistically significantly higher  SBP (mean (SD) 132 (19) than the patients with DAS &lt; 1.6 (remission) (mean (SD) 129 (20), p &lt; 0.01), and patients in LDAS but DAS≥1.6 had a statistically significantly higher SBP (mean (SD) 131 (19) than the patients in remission (mean (SD)  129 (20), p = 0.02) (Figure 1), whereas no association was found between DAS category and DBP. Gender, ACPA status or fulfilling the 2010 classification criteria did not influence the relation between DAS and blood pressure. Conclusions: In patients with RA or UA, a higher DAS is associated with higher blood pressure, but the clinical impact is unclear. Abstract Figure 1

scholarly journals FRI0136 PERIPHERAL PROTEIN BIOMARKER CHANGES FOLLOWING SELECTIVE INHIBITION OF JANUS KINASE 1 (JAK1) BY FILGOTINIB IN ADULTS WITH MODERATELY-TO-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WITH PRIOR INADEQUATE RESPONSE TO METHOTREXATE (FINCH1)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 650.2-651
Author(s):  
P. C. Taylor ◽  
E. Elboudwarej ◽  
B. Downie ◽  
J. Liu ◽  
R. E. Hawtin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Migration ◽  
Active Rheumatoid Arthritis ◽  
Immune Cell ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Bone Biology ◽  
Janus Kinase 1 ◽  
Immune Cell Migration ◽  
Dose Dependent

Background:Filgotinib (FIL), an oral selective Janus kinase 1 (JAK1) inhibitor has shown efficacy and safety in multiple phase 3 studies in adults with moderately-to-severely active rheumatoid arthritis (RA), including those with prior inadequate response to methotrexate (MTX) therapy (FINCH1;NCT02889796).Objectives:A longitudinal study of protein biomarkers related to JAK signaling1, bone biology2, immune cell migration2, and inflammation2was conducted to identify RA-associated markers altered by FIL vs MTX or adalimumab (ADA).Methods:FINCH1 RA patients (pts) were randomized to receive either a stable dose of MTX with placebo (PBO+MTX), ADA+MTX, and either FIL100mg+MTX or FIL200mg+MTX, once daily. Plasma, serum, and urine samples were taken from a subset of pts (~548) at baseline (BL) and weeks (wks) 4 and 12. Twenty-six pre-defined cytokines (biomarkers) were evaluated using ELISA. BL correlation between biomarkers and clinical response measures (DAS28CRP, SJC28, TJC28, CDAI, Patient Assessment and FACIT), were analyzed by Spearman Rank. Multiscale bootstrap resampling evaluated significant intra-cluster biomarker membership. Mean changes in biomarker levels from BL to wks 4 and 12 were compared between arms using PBO-adjusted estimates from a linear mixed effects model. A 5% false-discovery rate was applied for all analyses.Results:At BL, distinct biomarker-based pt clusters (CL) were identified. The strongest intra-group correlations were in bone-cartilage resorption/inflammation (CL1; Rho range 0.37–0.88) and JAK activity (CL2; Rho range 0.41–0.71). Individual BL cytokine levels were significantly associated with DAS28CRP, with unique biomarkers specific to various subcomponents of the score. Eleven biomarkers were associated with DAS28CRP, while 5, 3, and 2 were associated with CDAI, SJC28, and TJC28, respectively. The magnitude of FIL-associated treatment effects was time- and dose-dependent. Significant biomarker changes from BL were observed in FIL pts, relative to PBO+MTX pts. FIL100mg+MTX led to a significant change in 8 biomarkers by either 4 or 12 wks of treatment; FIL200mg+MTX significantly changed these and an additional 4 biomarkers by either time point. The greatest effect of FIL200mg+MTX was at 12 wks for CXCL13 (-38.4%) and IL6 (-53.7%). All treatment arms led to significant reductions in TNFα relative to PBO+MTX. FIL200mg+MTX treatment led to larger reductions of TNFα than ADA+MTX treatment at both wk4 (-24.7% vs -17.9%) and wk12 (-20.5% vs -12.2%), although the differences were not statistically significant.FIL and ADA caused differential patterns of cytokine response at either wks 4 or 12. Of 12 biomarkers with a significant FIL200mg+MTX treatment effect, there was a significantly larger reduction in TNFSF13B and CTX1 relative to ADA+MTX at 12 wks. Of 8 biomarkers with FIL100mg+MTX effects, only 2 (CXCL10 at wk 4; CXCL13 at wks 4 and 12) had significant differences from ADA+MTX. Relative either to FIL200mg+MTX or FIL100mg+MTX, and despite the same direction of effect, ADA+MTX led to a significantly larger reduction in CCL2, CXCL10, CCL4, and CXCL13.Conclusion:Compared with PBO, 12 wks of FIL treatment significantly reduced cytokines associated with JAK activity1, bone biology2, inflammation2, and immune cell migration2in MTX-IR pts. The effects were largely FIL dose-dependent; most cytokines exhibited similar effects regardless of treatment arms, but differential changes between FIL+MTX and ADA+MTX were observed, supportive of the different mechanisms of action of these therapies.References:[1]Majoros A, et al. Front Immunol. 2017;8:29[2]Brennan F, and McInnes I. J Clin Invest. 2008;118:3537-45Acknowledgments:This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Emon Elboudwarej Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Bryan Downie Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Jinfeng Liu Shareholder of: Gilead Sciences Inc., Roche, Employee of: Gilead Sciences Inc., Rachael E. Hawtin Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Amer M. Mirza Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc.

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