scholarly journals A.03 Durable clinical and MRI efficacy of alemtuzumab over 6 years in CARE-MS II patients with RRMS who relapsed between Courses 1 and 2

2018 ◽  
Vol 45 (s2) ◽  
pp. S10-S10
Author(s):  
MS Freedman ◽  
S Broadley ◽  
A Chinea ◽  
G Izquierdo ◽  
J Lycke ◽  
...  
Keyword(s):  
Disease Activity ◽  
Inadequate Response ◽  
Hyperintense Lesion ◽  
Prior Therapy ◽  
Brain Volume Loss ◽  
Disease Modifying Therapy ◽  
Core Study ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal ◽  
Relative Change

Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes over 2 years (y) versus SC IFNB-1a (CARE-MS II [NCT00548405]), with durable efficacy over a 4-y extension (NCT00930553). We present 6-y efficacy (2-y core study plus 4-y extension) in patients with relapse (relapsers) between Courses (C) 1 and 2. Methods: Annualized relapse rate (ARR); 6-month confirmed disability worsening (CDW); MRI disease activity (Gd-enhancing lesions; new/enlarging T2 hyperintense lesions); brain volume loss (BVL; derived by relative change in brain parenchymal fraction). Results: 105/435 (24%) patients relapsed between C1 and C2; 33% (relapsers) versus 55% without relapse (non-relapsers) received neither alemtuzumab retreatment nor another disease-modifying therapy through Y6. ARR (Y1: 1.2) declined post-C2 (0.5), remaining low through Y6 (0.2 [0.1, non-relapsers]; 10/105 [10%] relapsed). Through Y6, patients remained CDW-free (60% [relapsers]; 75% [non-relapsers]), Gd-enhancing lesion-free (94% [relapsers]; 90% [non-relapsers]), new/enlarging T2 hyperintense lesion-free (68% [relapsers]; 69% [non-relapsers]), and MRI disease activity-free (68% [relapsers]; 69% [non-relapsers]). Alemtuzumab slowed median percent yearly BVL (Y6: -0.13% [relapsers]; -0.10% [non-relapsers]). Conclusions: Patients relapsing between C1 and C2 improved post-C2 through Y6. These findings support administering 2 alemtuzumab courses to achieve optimal and durable benefit.

scholarly journals Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial

2021 ◽  
Vol 14 ◽  
pp. 175628642098213
Author(s):  
Alasdair J. Coles ◽  
Douglas L. Arnold ◽  
Ann D. Bass ◽  
Aaron L. Boster ◽  
D. Alastair S. Compston ◽  
...  
Keyword(s):  
Disease Activity ◽  
Disease Duration ◽  
Inadequate Response ◽  
Treatment Groups ◽  
Brain Volume Loss ◽  
Disease Modifying Therapy ◽  
Core Study ◽  
Treatment Naïve ◽  
Multiple Sclerosis Patients ◽  
Extension Trial

Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing–remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline. Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN–alemtuzumab), followed by additional, as-needed, alemtuzumab. Results: Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN–alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN–alemtuzumab patients; however, disability outcomes were less favorable versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups. Conclusion: This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups. ClinicalTrials.gov identifiers: NCT00530348; NCT00548405; NCT00930553

scholarly journals Alemtuzumab CARE-MS II 5-year follow-up

Neurology ◽  
2017 ◽  
Vol 89 (11) ◽  
pp. 1117-1126 ◽  
Author(s):  
Alasdair J. Coles ◽  
Jeffrey A. Cohen ◽  
Edward J. Fox ◽  
Gavin Giovannoni ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Incidence Rates ◽  
Continuous Treatment ◽  
Inadequate Response ◽  
Class Iii ◽  
Prior Therapy ◽  
Link Type ◽  
Brain Volume Loss ◽  
Core Study ◽  
Adjusted Incidence

Objective:To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy.Methods:In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed.Results:Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3–5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1–5: −0.48%, −0.22%, −0.10%, −0.19%, −0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter.Conclusions:Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment.Classification of evidence:This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.

scholarly journals P.027 Efficacy of a fourth alemtuzumab course in RRMS patients from CARE-MS II who experienced disease activity after three prior courses

2018 ◽  
Vol 45 (s2) ◽  
pp. S23-S23
Author(s):  
A Traboulsee ◽  
R Alroughani ◽  
A Boster ◽  
AD Bass ◽  
R Berkovich ◽  
...  
Keyword(s):  
Disease Activity ◽  
Inadequate Response ◽  
Expanded Disability Status Scale ◽  
Inclusion Criteria ◽  
Prior Therapy ◽  
Disease Modifying Therapy ◽  
Improved Outcomes ◽  
Disability Status ◽  
Disease Modifying ◽  
Edss Score

Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).

054 Disability improvement is observed in each functional system in alemtuzumab-treated patients with active RRMS: results from CARE-MS II extension

2018 ◽  
Vol 89 (6) ◽  
pp. A22.2-A22
Author(s):  
Richard AL Macdonell ◽  
Rany A Aburashed ◽  
Raed Alroughani ◽  
Dominique Dive ◽  
Guillermo Izquierdo ◽  
...  
Keyword(s):  
Functional System ◽  
Inadequate Response ◽  
Point Change ◽  
Prior Therapy ◽  
Link Type ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Bayer Healthcare ◽  
Core Study ◽  
Edss Score

IntroductionIn CARE-MS II (NCT00548405), alemtuzumab (12 mg/day, baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus subcutaneous interferon beta-1a over 2 years in relapsing-remitting MS patients with inadequate response to prior therapy; significantly greater percentage of alemtuzumab-treated patients achieved 6 month confirmed disability improvement (CDI). Efficacy remained durable in a 4 year extension (NCT00930553). Here we assess alemtuzumab efficacy on disability at the level of functional systems (FS) scores of the Expanded Disability Status Scale (EDSS) over 6 years.MethodsEDSS and individual FS scores were recorded at baseline and quarterly; CDI (≥1.0 point EDSS decrease confirmed over 6 months) was assessed in patients with baseline EDSS score ≥2.0.ResultsOf the 393 patients who entered the extension, 338 (86%) remained on study through Year 6; 50% received neither alemtuzumab retreatment nor other disease-modifying therapy after the initial 2 courses. Through Years 3–6, 76%–80% of patients showed stable (≤0.5 point change) or improved (≥1.0 point decrease) EDSS scores versus core study mean (SD) baseline score of 2.7 (1.2);≥75% were stable/improved in each FS. Through Year 6, 43% achieved 6 month CDI and 96% of patients with CDI had an EDSS score <4. 71% of patients with CDI achieved improvements in >1 FS. Improvements were observed in each FS, most frequently occurring in the sensory (48%), pyramidal (44%), and cerebellar (44%) systems; 21%–25% showed improvements in the brainstem, cerebral, visual, and bowel/bladder FS.ConclusionMost (86%) CARE-MS II patients who entered the extension remained on the study through Year 6;≥75% of alemtuzumab-treated patients had improved/stable scores across all FS over 6 years. Improvements were seen for each FS in patients with 6 month CDI, with 71% showing improvements in >1 FS, indicating a broad treatment effect with alemtuzumab on multiple aspects of disability improvements.Study supportSanofi and Bayer HealthCare Pharmaceuticals.

scholarly journals Grey matter atrophy is associated with disability increase in natalizumab-treated patients

2016 ◽  
Vol 23 (4) ◽  
pp. 556-566 ◽  
Author(s):  
Ethel Ciampi ◽  
Deborah Pareto ◽  
Jaume Sastre-Garriga ◽  
Angela Vidal-Jordana ◽  
Carmen Tur ◽  
...  
Keyword(s):  
Grey Matter ◽  
First Year ◽  
Volume Loss ◽  
Significant Volume ◽  
Brain Volume Loss ◽  
Lower Baseline ◽  
Brain Parenchymal Fraction ◽  
Left Caudate ◽  
Brain Parenchymal ◽  
Post Hoc

Background: Brain volume loss (BVL) is a key outcome in multiple sclerosis (MS) trials. Natalizumab is highly effective on inflammation with moderate impact on atrophy. Objective: To explore BVL in patients receiving natalizumab with an emphasis on grey matter (GM). Methods: We performed a retrospective post hoc analysis of BVL in 38 patients receiving natalizumab for 3 years using longitudinal voxel-based morphometry (VBM) and FreeSurfer. Results: Significant BVL was observed during first year: brain parenchymal fraction (BPF): −1.12% ( p < 0.001); white matter fraction (WMF): −0.9% ( p = 0.001); grey matter fraction (GMF): −1.28% ( p = 0.002). GM loss was found using VBM in bilateral cerebellum, cingulum, left > right fronto-parietal cortex, right > left hippocampus and left caudate. FreeSurfer showed significant volume losses in subcortical GM, brainstem and cerebellum, and cortical thinning in the left insula. In the second year, only WMF decrease (−0.6%; p = 0.015) was observed with no VBM changes, although FreeSurfer detected significant volume loss in thalamus, hippocampus and cerebellum. Baseline gadolinium enhancement influenced WMF and BPF changes during the first year, but not GMF. Patients with confirmed Expanded Disability Status Scale (EDSS) worsening at 3 years had lower baseline GMF and left thalamus volume and greater BVL over follow-up. Conclusion: BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability.

scholarly journals Characterisation of MS phenotypes across the age span using a novel data set integrating 34 clinical trials (NO.MS cohort): Age is a key contributor to presentation

2021 ◽  
pp. 135245852098863
Author(s):  
Frank Dahlke ◽  
Douglas L Arnold ◽  
Piet Aarden ◽  
Habib Ganjgahi ◽  
Dieter A Häring ◽  
...  
Keyword(s):  
Disease Activity ◽  
Brain Volume ◽  
Young Patients ◽  
Clinical Trial Data ◽  
Study Data ◽  
Phase Iii ◽  
Brain Images ◽  
Data Set ◽  
Brain Volume Loss ◽  
Phase Iii Study

Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective: The objective of this study is to describe the Novartis–Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes. Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients’ baseline age, using phase III study data (≈8000 patients). Results: NO.MS contains data of ≈35,000 patients (>200,000 brain images from ≈10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%–75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment. Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity.

scholarly journals MTX optimization or adding bDMARD equally improve disease activity in rheumatoid arthritis: results from the prospective study STRATEGE

Rheumatology ◽  
2021 ◽  
Author(s):  
Cécile Gaujoux-Viala ◽  
Christophe Hudry ◽  
Elena Zinovieva ◽  
Hélène Herman-Demars ◽  
René-Marc Flipo
Keyword(s):  
Disease Activity ◽  
Biological Treatment ◽  
Current Practice ◽  
Treatment Strategies ◽  
Route Optimization ◽  
Treat To Target ◽  
Inadequate Response ◽  
Inclusion Criteria ◽  
Treatment Optimization

Abstract Objectives The STRATEGE study aimed to describe treatment strategies in current practice in RA bDMARD-naive patients with an inadequate response to MTX therapy, and to compare clinical efficacy of the different therapeutic strategies on disease activity after six months. Methods Main inclusion criteria of this prospective, observational, multicentre study were confirmed RA diagnosis, treatment by MTX monotherapy, and need for therapeutic management modification. Results The 722 patients included had a mean (S.D.) RA duration of 5.3 (6.7) years, a mean DAS28 of 4.0 (±1.1); they were all receiving MTX monotherapy, 68% oral, at a mean dose of 15.0 (4.1) mg/wk. Two major strategies were identified: (i) MTX monotherapy dose and/or route optimization (72%) and (ii) bDMARD initiation ± MTX (16%). MTX dosing was modified for 70% of patients, maintained (dose and route) for 28% of patients, and interrupted for 2%. bDMARDs were started when the MTX mean dose was 17.4 mg/wk, 56% parenterally; MTX was maintained concomitantly for 96% of patients. Six-month follow-up results adjusted by propensity score showed that both options were equally successful in improving disease activity and physical function, with 63% and 68% of good-to-moderate EULAR responses, respectively. Conclusion The STRATEGE study shows the importance of initial MTX treatment optimization before initiation of a biological treatment and emphasizes the importance of treat-to-target strategy.

scholarly journals P128 A subgroup analysis of the efficacy of filgotinib for patients with moderately active RA following an inadequate response to methotrexate

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Maya H Buch ◽  
David Walker ◽  
Patrick D W Kiely ◽  
Christopher J Edwards ◽  
Jane Barry ◽  
...  
Keyword(s):  
Disease Activity ◽  
Short Form ◽  
Health Assessment ◽  
Physical Component Score ◽  
Inadequate Response ◽  
Research Support ◽  
Reactive Protein ◽  
American College Of Rheumatology ◽  
Moderate Disease ◽  
Sf 36

Abstract Background/Aims  Filgotinib is an oral, preferential janus kinase 1 inhibitor. FINCH 1 (NCT02889796) was a phase III, double-blind, placebo- and active-controlled study evaluating filgotinib efficacy and safety in patients with rheumatoid arthritis (RA) after inadequate response to methotrexate (MTX; MTX-IR). Methods  MTX-IR patients with moderately or severely active RA were randomised (3:3:2:3) to filgotinib 200 mg daily, filgotinib 100 mg daily, adalimumab 40 mg every 2 weeks, or placebo on a background of stable MTX for up to 52 weeks. An exploratory subgroup analysis of FINCH 1 was conducted in patients with moderately active RA based on Disease Activity Score in 28 joints with C-reactive protein (DAS28[CRP])&gt;3.2-≤5.1 at baseline. Proportion of patients achieving 20%/50%/70% improvement from baseline in American College of Rheumatology core criteria (ACR20/50/70), DAS28(CRP)≤3.2, DAS28(CRP)&lt;2.6, change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Physical Component Score (SF-36 PCS), patient-reported pain, and modified total Sharp/van der Heijde score (mTSS) were assessed at week (W)12 and W24. All analyses were exploratory without multiplicity adjustment; nominal P-values are reported. Results  Of 1,755 treated patients, 24% had moderate disease at baseline with similar proportions (21.9%-26.9%) across treatment groups. In each treatment arm, baseline characteristics were well balanced for the moderate disease activity subpopulation. The majority (77%) were female, mean (standard deviation [SD]) duration of RA was 7.8 (7.7) years; mean (SD) baseline DAS28(CRP) was 4.6 (0.42). At W12 and W24, proportions achieving ACR20/50/70, DAS28(CRP)&lt;2.6, and DAS28(CRP)≤3.2 were significantly higher for both filgotinib doses relative to placebo (Table). Improvement in HAQ-DI was significantly greater vs placebo at W12 but not W24 for both filgotinib doses (Table 1). For both doses of filgotinib vs placebo, SF-36 PCS and pain were significantly improved and there was numerically less radiographic progression as assessed by mTSS at W12 and W24 (Table). Composite disease activity, HAQ-DI, and mTSS scores with both filgotinib doses were comparable to adalimumab. P128 Table 1:Efficacy outcomes at week 12 and week 24Week 12Week 24FIL 200 mg (n = 104)FIL 100 mg (n = 121)ADA (n = 72)PBO (n = 128)FIL 200 mg (n = 104)FIL 100 mg (n = 121)ADA (n = 72)PBO (n = 128)ACR2077.9***67.8***65.343.872.1**75.2***68.154.7ACR5043.3***37.2***41.716.452.9***47.1**56.930.5ACR7019.2***17.4***15.33.932.7***29.8**29.213.3DAS28 (CRP)&lt;2.647.1***37.2***44.415.661.5***46.3***50.023.4DAS28 (CRP)≤3.267.3***63.6***66.739.174.0***73.6***62.549.2ΔHAQ-DI−0.51a,***−0.40b,*−0.47c−0.28d−0.57e−0.53f−0.65g−0.48hΔmTSS0.02i0.06j0.03k0.16l−0.04m,*0.11n−0.01o0.21pΔSF-36 PCS7.8q,***6.4r,***7.0s3.7t8.8u,**7.2v,*9.5w5.8xΔPain, mm−24***−23***−23−12−28***−28***−28−21***P&lt;0.001 vs PBO;**P&lt;0.01 vs PBO;*P&lt;0.05 vs PBO; all P-values are nominal. Binary efficacy endpoints were compared between FIL and PBO using Fisher's exact test. Comparisons of change from baseline between FIL vs PBO were conducted using mixed-effects models for repeated measures including treatment group, visit, treatment group by visit, baseline value as fixed effects, and subjects as random effect.an = 98;bn = 114;cn = 67;dn = 117;en = 89;fn = 108;gn = 61;hn = 100;in = 94;jn = 113;kn = 62;ln = 112;mn = 89;nn = 105;on = 60;pn = 97;qn = 99;rn = 116;sn = 67;tn = 118;un = 91;vn = 109;wn = 62;xn = 100.ΔHAQ-DI, change from baseline in Health Assessment Questionnaire-Disability Index; ΔmTSS, change from baseline in modified total Sharp/van der Heijde score; ΔSF-36 PCS, change from baseline in Short Form-36 Physical Component Score; ACR, American College of Rheumatology; ADA, adalimumab; DAS28(CRP), Disease Activity Score in 28 joints with C-reactive protein; FIL, filgotinib; PBO, placebo. Conclusion  In a subgroup of patients from FINCH 1 with baseline moderately active RA, significantly greater improvements in disease activity were observed with both filgotinib doses over placebo and associated with lower radiographic progression and reduced functional deficit. Disclosure  M.H. Buch: Consultancies; MHB reports serving as a consultant for AbbVie; Eli Lilly; Gilead Sciences, Inc.; Sandoz; Sanofi; and Serono. Grants/research support; MHB reports grants or research support from Pfizer, Roche, and UCB. D. Walker: Grants/research support; DW has received funding from Bristol-Myers Squibb; Eli Lilly; Gilead Sciences, Inc.; Novartis; and Pfizer, Inc. P.D.W. Kiely: Other; PK has attended advisory boards, been part of a speakers bureau, or received support to attend educational meetings from AbbVie, Gilead, Lilly, Novartis, and Sanofi. C.J. Edwards: Consultancies; CJE has provided consultancy for AbbVie; Biogen; Bristol-Myers Squibb; Celgene; Eli Lilly; Fresenius; Gilead Sciences, Inc.; GSK; Janssen; MSD; Mundipharma; Pfizer; Roche; Samsung; and Sanofi. Member of speakers’ bureau; CJE has served on speaker's bureaus for AbbVie; Biogen; Bristol-Myers Squibb; Celgene; Eli Lilly; Fresenius; Gilead Sciences, Inc.; GSK; Janssen; MSD; Mundipharma; Pfizer; Roche; Samsung; and Sanofi. Grants/research support; CJE reports grants from AbbVie; Biogen; Bristol-Myers Squibb; Celgene; Eli Lilly; Fresenius; Gilead Sciences, Inc.; GSK; Janssen; MSD; Mundipharma; Pfizer; Roche; Samsung; and Sanofi. J. Barry: Corporate appointments; JB is an employee of Gilead Sciences Ltd. G. McCaughey: Corporate appointments; GMcC is an employee of Gilead Sciences Ltd. L. Akroyd: Corporate appointments; LA is an employee of Gilead Sciences Ltd. I. Tiamiyu: Corporate appointments; IT is an employee of Gilead Sciences, Inc. L. Ye: Corporate appointments; LY is an employee of Gilead Sciences, Inc. K. Chen: Corporate appointments; KC is an employee of Gilead Sciences, Inc. P.C. Taylor: Consultancies; PCT has served as a consultant to AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Pfizer, BMS, Roche, Sanofi, Nordic Pharma, Fresenius, and UCB. Grants/research support; PCT reports research grants from Gilead Sciences, Inc.; Galapagos, and Celgene.

scholarly journals AB0330 HIGH REMISSION RATES IN RA – REAL LIFE DATA FROM BARITICINIB

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cox Regression ◽  
Real Life ◽  
Inadequate Response ◽  
Research Support ◽  
Das 28 ◽  
Patient Reported ◽  
One Year

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

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