FRI0138 THE IMPACT OF UPADACITINIB VERSUS METHOTREXATE OR ADALIMUMAB ON INDIVIDUAL AND COMPOSITE DISEASE MEASURES IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 651.1-652
Author(s):  
R. Van Vollenhoven ◽  
A. Ostor ◽  
E. Mysler ◽  
N. Damjanov ◽  
I. H. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Selective Inhibitor ◽  
Response Criteria ◽  
Research Support ◽  
Phase 3 ◽  
Once Daily ◽  
Composite Measures ◽  
Treatment Responses ◽  
The Impact ◽  
Mean Time

Background:In Phase 3 trials, upadacitinib (UPA), an oral JAK1-selective inhibitor, has been assessed as monotherapy vs MTX (SELECT-EARLY1) and in combination with MTX vs adalimumab + MTX (ADA; SELECT-COMPARE2) in RA pts who were MTX naïve or with inadequate responses to MTX (MTX-IR), respectively.Objectives:In this analysis we assessed individual and composite measures of disease activity in SELECT-EARLY and SELECT-COMPARE.Methods:In SELECT-EARLY, MTX-naïve pts received UPA 15 mg or 30 mg monotherapy once daily (QD), or MTX monotherapy, for 12 wks. In SELECT-COMPARE, MTX-IR pts on stable background MTX received UPA 15 mg QD, PBO, or ADA 40 mg every 2 wks for 12 wks. For this analysis, responses at Wk 12 were defined as ≥50% improvement in the 7 components of the ACR response criteria. Among ACR50 responders, the proportions of pts with ≥50% improvement in all 7 components of the ACR criteria was assessed. The proportion of pts achieving TJC68=0 and SJC66=0 was also determined. All analyses were based on observed data without imputation.Results:947 pts were randomized in SELECT-EARLY, and 1629 pts in SELECT-COMPARE. Mean time since RA diagnosis was 2.7 years in SELECT-EARLY (median 6 months) and 8.2 years in SELECT-COMPARE; mean DAS28(CRP) was 5.9 and 5.8, respectively. In SELECT-EARLY, significantly more MTX-naïve pts receiving UPA 15 mg or 30 mg monotherapy achieved ≥50% improvements in all ACR components at Wk 12 compared with MTX (Figure 1a,Figure 1b). In SELECT-COMPARE, significantly more MTX-IR pts on UPA 15 mg + MTX achieved ≥50% improvement in the ACR components vs PBO (all components) and ADA + MTX (all components except SJC and PhGA). Among pts with ACR50 responses at Wk 12, approximately half of the MTX-naïve pts on UPA 15 mg and 30 mg in SELECT-EARLY had ≥50% improvements in all 5 remaining ACR components (pain, PtGA, PhGA, HAQ-DI, hsCRP) compared with 28% with MTX. Corresponding proportions in MTX-IR pts in SELECT-COMPARE were 34% for UPA 15 mg + MTX, 28% for ADA + MTX, and 17% for PBO. UPA treatment also significantly increased the proportions of pts achieving both TJC68=0 and SJC66=0 vs PBO or MTX, and SJC66=0 vs ADA + MTX (Figure 1a,Figure 1b).Conclusion:In MTX-naïve and MTX-IR pts, treatment responses at 12 wks occurred in significantly higher proportions of pts receiving UPA monotherapy vs MTX and UPA + MTX vs PBO for all 7 components of the ACR response criteria, and for 5 of 7 ACR components for UPA + MTX vs ADA + MTX. Favorable outcomes with UPA treatment were evident both in composite and individual parameters.References:[1]van Vollenhoven R, et al. Arthritis Rheumatol 2018;70(Suppl. 10): Abstract 891[2]Fleischmann R, et al. Arthritis Rheumatol 2018;70(Suppl. 10): Abstract 890Disclosure of Interests:Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Andrew Ostor Consultant of: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Speakers bureau: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., 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

scholarly journals POS0492 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER PREDICTS THE LIKELIHOOD OF EULAR NON-RESPONSE TO TNF INHIBITOR THERAPIES IN RA: RESULTS FROM A RETROSPECTIVE COHORT ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 478.2-479
Author(s):  
L. Zhang ◽  
C. van der Tog ◽  
A. den Broeder ◽  
T. Mellors ◽  
E. Connolly-Strong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Predictive Value ◽  
Molecular Signature ◽  
Response Criteria ◽  
Treat To Target ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Target Setting ◽  
The Impact

Background:Following RA treatment recommendations, most people with rheumatoid arthritis (RA) begin targeted therapy with TNF inhibitors (TNFi), even though inadequate response to TNFi therapies is widespread. Treatment changes from one medication to the next are currently fueled by disease-activity measures and eventually result in disease control for most patients; however, this “trial-and-error” approach wastes precious time on ineffective treatments. A delay in reaching treat-to-target goals has a negative effect on patient burden and, possibly, disease progression.1 Useful predictors for TNFi response have been challenging to identify but a specific molecular signature response classifier (MSRC) test was shown to be predictive for inadequate response to TNFi therapies.2 The impact of such identification has the potential to result in improved patient outcomes, but further validation would be welcome, especially for response criteria other than ACR50, and in a stringent treat-to-target setting with lower baseline disease activity.Objectives:To validate the predictive value of the MSRC test in identifying those patients who do not meet EULAR good response criteria after 6 months of TNFi treatment.Methods:Data from a prospective cohort study conducted in the Sint Maartenskliniek (Nijmegen, the Netherlands) of RA patients who started adalimumab or etanercept TNFi as their first biologic were included.3 Baseline RNA samples and clinical assessments were used to identify patients who had a molecular signature1 of non-response to TNFi therapy. Outcomes were calculated at six months using DAS28-CRP-based EULAR good response, and high and low confidence responders and non-responders were identified using Monte Carlo simulation with 2,000 repeats and 70% precision cut off. Outcome measurements were blinded for test results. Treatment switch before 6 months was imputed as non-response. Odds ratios and area under the ROC curve (AUC) assessments were used to evaluate the ability of the MSRC test to predict inadequate response at 6 months against EULAR good response criteria.Results:A total of 68 out of 88 RA patients were identified to have a high-confidence response status and were included in analyses (Table 1). EULAR good response was observed in 45.5% (31/68) of patients. Patients were stratified according to detection of a molecular signature of non-response with an AUC of 0.61. The odds that a patient with the molecular signature of non-response at baseline failed to achieve a EULAR good response at 6 months was four times greater than that of a patient lacking the molecular signature (odds ratio 4.0, 95% confidence interval 1.2-13.3).Table 1.Patient demographicsCharacteristicRA patients (N = 68)Age, median (SD)57 (11)Female, n (%)43 (63.2)CCP positive, n (%)34 (50.0)RF positive, n (%)38 (55.9)Prescribed adalimumab at baseline, n (%)11 (16.2)Prescribed etanercept at baseline, n (%)57 (83.8)Conclusion:In this validation study, the molecular signature of non-response identified patients who did not fulfill the EULAR good response criteria to TNFi therapies. The patient selection process for this study had limitations; additional analysis in an alternative cohort would further verify the performance of the MSRC test. Nevertheless, the test, previously validated for ACR50, now has been validated using EULAR good response in a treat-to-target setting.References:[1]Schipper LG et al, Time to achieve remission determines time to be in remission. Arthritis Res Ther 201[2]Mellors T, et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine 2020[3]Tweehuysen L et al. Predictive value of ex-vivo drug-inhibited cytokine production for clinical response to biologic DMARD therapy in rheumatoid arthritis. Clin Exp Rheumatol 2019Disclosure of Interests:Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Celeste van der Tog: None declared, Alfons den Broeder Consultant of: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Grant/research support from: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

scholarly journals Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis—a comprehensive review

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Paul Emery ◽  
Patrick Durez ◽  
Axel J. Hueber ◽  
Inmaculada de la Torre ◽  
Esbjörn Larsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Janus Kinase ◽  
X Rays ◽  
Phase 3 ◽  
Once Daily ◽  
Positive Effects ◽  
Damage Progression ◽  
Structural Joint

AbstractBaricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.

SAT0149 EXPOSURE-RESPONSE RELATIONSHIPS FOR EFFICACY AND SAFETY OF FILGOTINIB AND ITS METABOLITE GS-829845 IN SUBJECTS WITH RHEUMATOID ARTHRITIS BASED ON PHASE 2 AND PHASE 3 STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1013-1014
Author(s):  
A. Meng ◽  
K. Anderson ◽  
C. Nelson ◽  
B. Kirby ◽  
L. Ni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Response Rates ◽  
High Response ◽  
Phase 2 ◽  
Phase 3 ◽  
Once Daily ◽  
Exposure Response ◽  
Serious Infections ◽  
Wide Range ◽  
Grade 3

Background:Filgotinib is an orally administered small molecule that provides selective inhibition of JAK1, a signaling molecule that helps drive inflammatory pathways underlying rheumatoid arthritis (RA).Objectives:Exposure-response (ER) analyses were performed for efficacy following completion of Phase 2 studies over a wide range of doses to support evaluation of 200mg and 100 mg once daily in Phase 3 studies. ER analyses were subsequently performed by using Phase 3 efficacy data to support selection of the proposed registrational dose. ER analyses for safety based on pooled Phase 2 and Phase 3 studies were conducted to examine the safety of evaluated doses.Methods:Population PK analyses were conducted to estimate plasma exposures of filgotinib and GS-829845 (major circulating active metabolite of filgotinib) in both Phase 2 (DARWIN 1 and DARWIN 2) and Phase 3 studies (FINCH 1, FINCH 2, and FINCH 3) encompassing a dose range of 25 to 100 mg twice daily and 50 to 200 mg once daily. As both filgotinib and GS-829845 contribute to efficacy via JAK1 inhibition, their exposures were combined into single parameters, AUCeff and Ctau-eff (effective area under the curve and effective concentration at trough, by accounting for relative inhibition potency and molecular weight) in the ER analyses for various efficacy endpoints (e.g ACR20/50/70 responses) at Week 12 and Week 24. The ER analyses for safety endpoints (the 5 most frequent treatment-emergent adverse events [TEAEs] and Grade 3 or 4 laboratory abnormalities, serious TEAEs, and serious infections) were performed separately for filgotinib and GS-829845 exposures to characterize the individual safety profile of each analyte. The 5 evaluated TEAEs were nausea, nasopharyngitis, upper respiratory tract infection, headache, and hypertension; the 5 Grade 3/4 laboratory abnormalities included lymphocytes decrease, glucose increase, phosphate decrease, triacylglycerol lipase increase, and creatine kinase increase.Results:In the ER analyses for efficacy based on Phase 2 studies, high response rates were demonstrated in ACR20/50/70 across all octile groups in subjects with RA receiving filgotinib and the ER supported further evaluation of both 200 mg and 100 mg once daily doses in Phase 3 clinical studies. Similarly, ER relationships based on pooled Phase 3 studies across various endpoints (e.g ACR20/50/70) consistently revealed high response rates across the exposure range for both the filgotinib 200 mg and 100 mg doses. A trend of increasing response with increasing exposure was observed over the exposure range for multiple secondary efficacy endpoints including ACR50 and ACR70 with the effective exposures at filgotinib 200 mg primarily residing on the plateau of the ER curves.Filgotinib was generally well-tolerated with no individual TEAE or Grade 3 or 4 laboratory abnormality > 5% in the filgotinib 200 mg once daily group up to Week 12. No relationships were observed between filgotinib and GS-829845 exposures (AUC0-24 and Cmax) and the most frequent TEAEs, Grade 3/4 laboratory abnormalities, serious TEAEs, or serious infections up to Week 52.Conclusion:ER analyses demonstrate that both the 200 mg and 100 mg once daily filgotinib doses are efficacious in subjects with moderately to severely active RA without clear dose-dependent effects on safety. The trend towards greater efficacy with higher exposures for some secondary endpoints (ACR50 and ACR70) and a lack of exposure-safety relationship supports a dose of 200 mg once daily over 100 mg once daily since it presents the best benefit/risk ratio among the doses tested.Disclosure of Interests: :Amy Meng Shareholder of: Gilead Sciences, Employee of: Gilead, Kacey Anderson Shareholder of: Gilead Sciences, Employee of: Sciences, Cara Nelson Shareholder of: Gilead, Employee of: Gilead, Brian Kirby Shareholder of: Gilead, Employee of: Gilead, Liyun Ni Shareholder of: Gilead, Employee of: Gilead, Shu-Min Chuang Shareholder of: Gilead, Employee of: Gilead, Brian Kearney Shareholder of: Gilead, Employee of: Gilead, Anita Mathias Shareholder of: Gilead, Employee of: Gilead

scholarly journals Exposure-Response Relationships for Efficacy and Safety of Filgotinib and its metabolite GS-829845 in Subjects with Rheumatoid Arthritis Based on Phase 2 and Phase 3 Studies

2021 ◽  
Author(s):  
Amy Meng ◽  
Kacey Anderson ◽  
Cara Nelson ◽  
Liyun Ni ◽  
Shu-Min Chuang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Therapeutic Effects ◽  
Phase 2 ◽  
Phase 3 ◽  
Two Phase ◽  
Once Daily ◽  
Exposure Response ◽  
Daily Dose

Aims:Filgotinib is a potent, oral, JAK1-preferential inhibitor for the treatment of rheumatoid arthritis (RA). This report describes exposure-response (ER) analyses of filgotinib for dose confirmation based on three Phase 3 and two Phase 2 studies in moderate to severe RA patients. Methods:The PK exposures used in ER analyses were derived from population pharmacokinetic analysis. The relationship between filgotinib exposures and various efficacy endpoints (ACR20/50/70 and DAS28) was assessed over octile groups of exposures by using combined exposures of filgotinib and GS-829845 (major, active metabolite). For the ER analyses of safety, exposures were examined between subjects who experienced and who did not experience the evaluated safety events, which was conducted separately for filgotinib and GS-829845. Results:Exposure efficacy relationships consistently revealed high response rates across the exposure range for filgotinib 200 mg once daily dose. A trend of increasing response with increasing exposure was observed over the exposure range for the primary and multiple secondary efficacy endpoints, with exposures associated with the 200 mg dose primarily residing on the curve plateau. For exposure-safety analyses, filgotinib and GS-829845 exposures were similar irrespective of presence/absence of the evaluated safety endpoints, indicating no exposure-safety relationship for common TEAEs, common laboratory abnormalities, serious TEAEs, or serious infections. Conclusions:ER analyses confirmed that filgotinib produced more robust therapeutic effects across the exposure range observed at 200 mg once daily compared to lower doses. The positive exposure-efficacy relationship and a lack of exposure-safety relationship on the evaluated safety endpoints supported the 200 mg once daily dose for commercialization.

P209 Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the select Phase 3 clinical programme

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Stanley B Cohen ◽  
Ronald van Vollenhoven ◽  
Kevin Winthrop ◽  
Cristiano Zerbini ◽  
Yoshiya Tanaka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Profile ◽  
Clinical Signs ◽  
Integrated Analysis ◽  
Inadequate Response ◽  
Research Support ◽  
Phase 3 ◽  
Research Grants ◽  
Treatment Groups ◽  
All Treatment

Abstract Background Upadacitinib (UPA), a JAK1-selective inhibitor, significantly improved clinical signs and symptoms of rheumatoid arthritis (RA) in patients naïve to methotrexate (MTX) and with an inadequate response to conventional synthetic DMARDs (csDMARD-IR) or biologic DMARDs (bDMARD-IR). The objective was to assess the safety of UPA as monotherapy (mono) and as combination therapy with background csDMARDs in patients with moderately to severely active RA from the safety database of the Phase 3 clinical programme. Methods Treatment-emergent adverse events (TEAEs) from 5 pivotal, randomised, double-blind, controlled Phase 3 trials of UPA 15 mg or 30 mg QD in RA patients were analysed using integrated short-term (ST), individual studies with long-term (LT) active comparator and integrated LT (all Phase 3 exposure; E/100PY) analyses sets. Results Across the Phase 3 trials, 3834 patients received ∼1 dose of UPA 15 mg (n = 2630) or 30 mg QD (n = 1204) »4020.1 PY of UPA exposure with no option to switch doses. The ST frequencies of overall SAEs and AEs leading to discontinuation were low, but higher on both UPA doses vs PBO. LT event rates were similar on UPA 15 mg vs ADA and slightly higher on UPA vs MTX mono. Deaths occurred in all treatment groups. Serious infection (SIEs) frequencies were higher on both UPA doses vs PBO. SIE rates on both UPA doses were higher vs MTX, but similar on UPA 15 mg vs ADA. Herpes zoster (HZ) frequencies and rates were higher on both UPA doses vs PBO, and vs MTX, ADA, respectively. The rates of SIE and HZ were higher on UPA 30 vs 15 mg. Adjudicated MACE were reported in all treatment groups including PBO. LT MACE rates were similar on UPA 15 mg and ADA and on UPA 15 mg and MTX mono, but higher on UPA 30 mg mono (low number of events, 2-4 per set). Adjudicated VTEs occurred at comparable frequencies on UPA vs PBO and at comparable rates on UPA vs active comparators. Malignancy (excluding non-melanoma skin cancer [NMSC]) rates were similar on UPA vs MTX, UPA 15 mg vs ADA, and 15 vs 30 mg. The NMSC rates on UPA 15 mg and ADA were similar; the rate on 30 mg was higher than 15 mg, but both UPA NMSC rates were in the range reported for RA patients treated with DMARDS. The standardised incidence ratio (95% CI) for malignancy (15 mg: 0.98 [0.61, 1.49], 30 mg: 1.49 [0.85, 2.42]) was not elevated vs the general population. Conclusion Treatment with UPA increased the risk of SIE and HZ, but not those of VTE, MACE, and malignancy vs comparators. These data support that UPA has an acceptable safety profile in the treatment of moderately to severely active RA. Disclosures S.B. Cohen: Grants/research support; Received grants and personal fees from Amgen, Abbvie, Boehringer Ingelheim, Pfizer and Sandoz. R. van Vollenhoven: Consultancies; AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB. Grants/research support; Received grants from AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Lilly, Pfizer, and UCB. K. Winthrop: Consultancies; Received consulting fees and research grants from UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, AbbVie, and Roche. C. Zerbini: Consultancies; Merck, Pfizer, Sanofi-Aventis and Pfizer. Grants/research support; Received research grants from Amgen, GSK, Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis, Servier and Roche. Y. Tanaka: Honoraria; Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, Abbvie, Pfizer, YL Biologics, Bristol-Myers, Glaxo-Smithkline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen, Asahi-kasei. Grants/research support; Mitsubishi-Tanabe, Bristol-Myers, Eisai, Chugai, Takeda, Abbvie, Astellas, Daiichi-Sankyo, Ono, MSD, Taisho-Toyama. L. Bessette: Grants/research support; Speaking fees, consulting fees, and research grants from Amgen, BMS, Janssen, Roche, UCB Pharma, AbbVie Inc, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, and Novartis. Y. Zhang: Corporate appointments; Employee of AbbVie. N. Khan: Corporate appointments; Employee of AbbVie. B. Hendrickson: Corporate appointments; Employee of AbbVie. J.V. Enejosa: Corporate appointments; Employee of AbbVie. G. Burmester: Honoraria; Received speaking or consulting fees from AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma.

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

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

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

scholarly journals OP0131 ANIFROLUMAB EFFECTS ON RASH AND ARTHRITIS IN PATIENTS WITH SLE AND IMPACT OF INTERFERON SIGNAL IN POOLED DATA FROM PHASE 3 TRIALS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 75-76
Author(s):  
J. T. Merrill ◽  
V. Werth ◽  
R. Furie ◽  
E. F. Morand ◽  
J. M. Kahlenberg ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cutaneous Lupus Erythematosus ◽  
Small Sample ◽  
Type I ◽  
Research Support ◽  
Phase 3 ◽  
Pooled Data ◽  
Link Type ◽  
The Impact

Background:Treatment with the type I interferon (IFN) receptor antibody anifrolumab was associated with clinical improvements in mucocutaneous and musculoskeletal disease activity in patients with systemic lupus erythematosus (SLE) in the phase 2 MUSE trial (NCT01438489) and phase 3 TULIP trials.1–4 Because rash and arthritis are the most common manifestations of SLE, the effect of anifrolumab on these symptoms can be examined in biomarker-defined subsets, as previously reported for the MUSE trial.2Objectives:To evaluate the effect of anifrolumab on rash and arthritis in patients with SLE, and the impact of IFN gene signature (IFNGS) on treatment response, using disease measures of different stringency in pooled data from the phase 3 TULIP trials.Methods:TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were placebo-controlled, 52-week trials of intravenous anifrolumab administered every 4 weeks in patients with moderate to severe SLE.3,4 In this post hoc analysis, outcomes of rash and arthritis were evaluated using mucocutaneous and musculoskeletal domains of the SLE Disease Activity Index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) index. In addition, the modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) score was used to evaluate rash, and tender and swollen joint counts were used to assess arthritis.Results:360 patients received anifrolumab 300 mg (IFNGS test–high, n=298; IFNGS test–low, n=62) and 366 patients were given placebo (IFNGS test–high, n=302; IFNGS test–low, n=64). Change from baseline to Week 52 compared with placebo was measured by outcomes, ordered by their stringency. More anifrolumab-treated patients achieved rash improvement using SLEDAI-2K (complete resolution: difference 13.5%, nominal P<0.001), BILAG (at least 1 severity grade lowering: difference 15.5%, nominal P<0.001), and mCLASI (≥50% improvement, if baseline score >0: difference 15.6%, nominal P<0.001). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 17.0%, nominal P<0.001, BILAG: difference 16.1%, nominal P<0.001; mCLASI: difference 18.1%, nominal P<0.001). There was a trend toward anifrolumab-associated rash improvement in IFNGS test–low patients using BILAG (Figure). More patients receiving anifrolumab had SLEDAI-2K–defined resolution in arthritis (difference 8.2%, nominal P=0.029), BILAG severity lessening (difference 11.8%, nominal P=0.002), and ≥50% decrease in tender/swollen joint counts, when ≥6 at baseline (difference 12.6%, nominal P=0.016). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 11.7%, nominal P=0.005; BILAG: difference 12.9%, nominal P=0.003; joint counts: difference 11.3%, nominal P=0.054). In IFNGS test–low patients, there was a trend toward anifrolumab-associated arthritis improvement when measured using BILAG, and the effect of anifrolumab on the number of swollen/tender joint counts was similar to the IFNGS test–high group, although the IFNGS test–low sample size in this analysis was very small (Figure).Conclusion:In pooled data from the TULIP trials, anifrolumab treatment was associated with improvements in rash and arthritis using measures of different stringency. The SLEDAI-2K findings were largely driven by the subset of patients who were IFNGS test–high. However, using measures that were more sensitive to change, despite small sample sizes, IFNGS test–low patients may also have benefit.References:[1]Furie R, et al. Arthritis Rheumatol. 2017;69:376–86.[2]Merrill JT, et al. Lupus Sci Med. 2018;5:e000284.[3]Furie RA, et al. Lancet Rheumatol. 2019;1:e208–19.[4]Morand EF, et al. N Engl J Med. 2020;382:211–21.Acknowledgements:Writing assistance by Victoria Alikhan, PhD, of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca.Disclosure of Interests:Joan T Merrill Consultant of: AstraZeneca, AbbVie, Amgen, Aurinia, BMS, EMD Serono, GSK, Remegen, Janssen, Provention, and UCB, Grant/research support from: BMS and GSK, Victoria Werth Speakers bureau: University of Pennsylvania, who own the copyright for the CLASI and SDASI, Consultant of: AbbVie, Amgen, Argenx, AstraZeneca, Biogen, BMS, Celgene, Chrysalis, CSL Behring, Cugene, Eli Lilly, EMD Serono, Genentech, GSK, Incyte, Idera, Janssen, Kirin, Medimmune, Medscape, Nektar, Octapharma, Pfizer, Principa, Regeneron, Resolve, and Viela Bio, Grant/research support from: AstraZeneca, Biogen, Celgene, Corbus Pharmaceuticals, Genentech, Gilead, Janssen, Pfizer, Syntimmune, and Viela Bio, Richard Furie Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, J Michelle Kahlenberg Consultant of: Admirex Pharmaceuticals, AstraZeneca, Aurinia Pharmaceuticals, BMS, Boehringer Ingelheim, Eli Lilly, and Ventus Therapeutics, Grant/research support from: BMS/Celgene and Q32 Bio, Gabriel Abreu Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca

scholarly journals POS1175 ASSESSMENT OF THE COVID-19 PANDEMIC FROM THE PERSPECTIVE OF PEOPLE WITH RHEUMATIC MUSCULOSKELETAL DISEASES IN EUROPE. RESULTS FROM THE REUMAVID STUDY (PHASE 1)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 868-869
Author(s):  
M. Garrido-Cumbrera ◽  
H. Marzo-Ortega ◽  
J. Correa-Fernández ◽  
S. Sanz-Gómez ◽  
L. Christen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mental Health ◽  
United Kingdom ◽  
Axial Spondyloarthritis ◽  
Musculoskeletal Diseases ◽  
Categorical Variables ◽  
Research Support ◽  
Health Crisis ◽  
The United Kingdom ◽  
The Impact

Background:The COVID-19 pandemic is an unprecedented public health crisis affecting people worldwide, including those with rheumatic and musculoskeletal diseases (RMDs).Objectives:REUMAVID aims to assess the impact of the COVID-19 pandemic and lockdown on the wellbeing, mental health, disease activity and function, access to health care and treatment, support services, and hopes and fears of people RMDs.Methods:REUMAVID is an international collaboration led by the Health & Territory Research group at University of Seville, Spain, together with a multidisciplinary team including patient organization and rheumatologists. This cross-sectional study consisting of an online survey gathering data from patients with a diagnosis of 15 RMDs in Cyprus, France, Greece, Italy, Portugal, Spain and the United Kingdom. Participants are recruited by patient organizations. Data is collected in two phases: 1) during the first peak of the COVID-19 pandemic (Spring 2020), and 2) as a follow-up to the pandemic (Winter 2020). This analysis presents descriptive results of the aggregated data, summarizing continuous and categorical variables.Results:A total of 1,800 RMD patients have participated in the first wave of the COVID-19 pandemic (from early April to mid-June 2020). The most frequent reported diagnosis were axial spondyloarthritis (37.2%), rheumatoid arthritis (29.2%) and osteoarthritis (17.2%). Mean age was 52.6±13.2, 80.1% were female, 69.6% were in a relationship or married and 48.6% had university studies. In total, 1.1% had tested positive for COVID-19, 10.8 % reported symptoms but were not tested, while 88.1% did not experience any symptoms. 46.6% reported worsening health during the pandemic. 63.9% perceived their health status to be “fair to very bad”. Access to care was limited with 58.4% being unable to keep the rheumatologist appointment, of which, 35.2% were cancelled by the provider and 54.4% was attended by phone or online. 15.8% changed their medication, for which 65.5% were changed by the provider and 24.6% by own decision. Reported wellbeing and psychological health during the pandemic was poor, with 49.0% reporting poor wellbeing according to the WHO-5 scale, 57.3% marking as anxiety and 45.8% as depression in the HADS scale. During the pandemic, 24.6% smoked and 18.2% drank more than before and 54.5% were unable to exercise at home.Conclusion:Results from the first phase of REUMAVID show disturbance of the healthcare quality, substantial changes in harmful health behaviors and an unprecedented impairment of mental health in REUMAVID participants. REUMAVID will continue to collect information in order to assess the impact of the COVID-19 pandemic in people affected by RMDs across Europe.Acknowledgements:This study was supported by Novartis Pharma AG. We would like to thank all patients that completed the survey as well as all of the patient organisations that participated in the REUMAVID study including: the Cyprus League Against Rheumatism (CYPLAR) from Cyprus, the Association Française de Lutte Anti-Rhumatismale (AFLAR) from France, the Hellenic League Against Rheumatism (ELEANA) from Greece, the Associazione Nazionale Persone con Malattie Reumatologiche e Rare (APMARR) from Italy, the Portuguese League Against Rheumatic Diseases (LPCDR), from Portugal, the Spanish Federation of Spondyloarthritis Associations, the Spanish Patients’ Forum (FEP), UNiMiD, Spanish Rheumatology League (LIRE), Andalusian Rheumatology League (LIRA), Catalonia Rheumatology League and Galician Rheumatology League from Spain, and the National Axial Spondyloarthritis Society (NASS), National Rheumatoid Arthritis (NRAS) and Arthritis Action from the United Kingdom.Disclosure of Interests:Marco Garrido-Cumbrera: None declared, Helena Marzo-Ortega Speakers bureau: AbbVie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB, Consultant of: AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB, Grant/research support from: Janssen and Novartis, José Correa-Fernández: None declared, Sergio Sanz-Gómez: None declared, Laura Christen Employee of: Novartis Pharma AG, Victoria Navarro-Compán Grant/research support from: Abbvie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB.

SAT0123 TREATMENT SATISFACTION, EXPECTATIONS, PATIENT PREFERENCES AND CHARACTERISTICS, INCLUDING DIGITAL HEALTH LITERACY (DHL), AND THE IMPACT OF SUBOPTIMAL DISEASE CONTROL IN A LARGE INTERNATIONAL COHORT OF PATIENTS WITH RHEUMATOID ARTHRITIS (RA): THE SENSE STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 996-997
Author(s):  
P. C. Taylor ◽  
C. Ancuta ◽  
O. Nagy ◽  
M. Delavega ◽  
A. Gordeev ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Control ◽  
Patient Preferences ◽  
Joint Pain ◽  
Treatment Satisfaction ◽  
Eligible Patient ◽  
Inadequate Response ◽  
Research Support ◽  
Increased Risk ◽  
The Impact

Background:Patient characteristics, their treatment preferences and goals are important determinants of treatment success in rheumatoid arthritis (RA).Objectives:SENSE study aimed at assessing the impact of inadequate response to disease-modifying anti-rheumatic drugs on disease outcomes, and analyze their attitude, their treatment and disease.Methods:Non-interventional, cross-sectional study conducted in 18 countries in Europe, Asia, and America. Adult RA patients with moderate/high disease activity were eligible. Patient satisfaction was assessed by Treatment Satisfaction Questionnaire for Medication, Version 1.4 (TSQM v1.4). Treatment adherence, patient preferences, and expectations were evaluated by visual analog scale. eHealth Literacy Scale was employed for evaluating DHL. Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis, v2.0 (WPAI-RA) was used to assess workability and patient documentation for healthcare resource utilization (HRU).Results:1624 patients were included in this analysis; most were female (84.2%), middle-aged, and had a mean (standard deviation [SD]) disease duration of 10.5 (9.3) years. 11.9% of the patients had retired early and 6.0% were unemployed due to RA. Mean (SD) total WPAI-RA score was 55.1% (26.7). In the previous 3 months, the mean (SD) number of healthcare professional and emergency room visits were 2.2 (2.5) and 1.6 (1.3), respectively. Mean (SD) TSQM v1.4 global satisfaction subscore was 60.9 (20.9), with only 13.5% reporting good treatment satisfaction (TSQM global ≥80). The leading treatment expectations were ‘general improvement of arthritis’, ‘less joint pain’, and ‘lasting relief of RA symptoms,’ with mean (SD) scores of 5.7 (1.6–1.7) for each. 60.7% of patients preferred oral administration and 31.3% preferred not to use drug combinations for RA. Preferred time to effect was predominantly ‘up to one week’ (71.1%). Least frequently side effects rated ‘acceptable’ were ‘increased risk for malignancies’ (3.5%) and ‘increased risk for cardiovascular diseases’ (3.3%). Most patients (67.4%) had poor DHL. Good adherence (in 87.4% of patients) was significantly associated with lower levels of joint pain.Conclusion:Suboptimal disease control has a significant impact on satisfaction, workability, and HRU. Our results can support shared decision-making when setting RA treatment strategy.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, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Orsolya Nagy Shareholder of: AbbVie, Employee of: AbbVie, Maria DeLaVega: None declared, Andrey Gordeev Speakers bureau: AbbVie, Eli Lilly, Pfizer, Sanofi, Bristol-Myers Squibb, Merck Sharpe and Dohme, Roche, and UCB., Radka Jankova Speakers bureau: AbbVie, Eli Lilly, Pfizer, Sanofi, Bristol-Myers Squibb, Merck Sharpe and Dohme, Roche, and UCB, Umut Kalyoncu Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB., Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB., Ivan Lagunes-Galindo Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jadranka Morovic-Vergles Speakers bureau: Abbvie., Roche, MSD, Eli Lilly, Pfizer, Mylan, Amgen, Fresenius Kabi, Mariana Peixoto GU e Silva de Souza Grant/research support from: AbbVie, UCB, Bristol-Myers Squibb, Pfizer, and GSK, Consultant of: AbbVie, Roche, UCB, Pfizer, and Jansen, Speakers bureau: AbbVie, Roche, UCB, Pfizer, and Jansen, Bernadette Rojkovich: None declared, Prodromos Sidiropoulos: None declared, Atsushi Kawakami: None declared

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