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 Alemtuzumab CARE-MS I 5-year follow-up

Neurology ◽  
2017 ◽  
Vol 89 (11) ◽  
pp. 1107-1116 ◽  
Author(s):  
Eva Havrdova ◽  
Douglas L. Arnold ◽  
Jeffrey A. Cohen ◽  
Hans-Peter Hartung ◽  
Edward J. Fox ◽  
...  
Keyword(s):  
Incidence Rates ◽  
Continuous Treatment ◽  
Thyroid Disorder ◽  
Class Iii ◽  
The Core ◽  
Link Type ◽  
Brain Volume Loss ◽  
Core Study ◽  
Treatment Naïve ◽  
Adjusted Incidence

Objective:To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348).Methods:Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included 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).Results:Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0–5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2–4, remaining low in year 5 (years 1–5: −0.59%, −0.25%, −0.19%, −0.15%, and −0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined.Conclusions:Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses.ClinicalTrials.gov identifier:NCT00530348; NCT00930553.Classification of evidence:This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.

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.

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 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 Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 629-639 ◽  
Author(s):  
Mark C. Genovese ◽  
César Pacheco Tena ◽  
Arturo Covarrubias ◽  
Gustavo Leon ◽  
Eduardo Mysler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Incidence Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

ALEMTUZUMAB IMPROVES 3-YEAR QUALITY OF LIFE IN CARE-MS II

2015 ◽  
Vol 86 (11) ◽  
pp. e4.9-e4
Author(s):  
Alasdair Coles ◽  
Gavin Giovannoni ◽  
Thibault Moreau ◽  
Eva Havrdova ◽  
David Margolin ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Short Form ◽  
Extension Study ◽  
Prior Therapy ◽  
Link Type ◽  
Relapsing Remitting ◽  
Emotional Aspects ◽  
Relapsing Remitting Multiple Sclerosis

In the 2-year, phase 3 CARE–MS II study (NCT00548405) of relapsing-remitting multiple sclerosis (RRMS) patients with inadequate efficacy response to prior therapy, alemtuzumab demonstrated superior efficacy and quality-of-life (QoL) improvements versus subcutaneous interferon beta-1a, with manageable safety. Here, QoL outcomes are examined in alemtuzumab-treated patients at Year 3 in an ongoing extension study (NCT00930553). 393 of 435 alemtuzumab 12 mg-treated patients entered the extension study; 80 received as-needed alemtuzumab retreatment during Year 3. Mean Functional Assessment of multiple sclerosis total score (scale 0–176) improved from baseline to year 3 (119.1 vs 124.8; P<0.0001), with 5 of 6 subscales significantly improved. Mean Short-Form 36–Item survey physical and mental component summary scores (scale 1–100) rose from baseline to Year 3 (42.7 vs 44.7; P<0.0001, and 44.9 vs 46.5; P=0.042, respectively), with 6 of 8 subscales improved, and 82% and 73% of patients, respectively, having a stable or improved score at Year 3. EuroQol 5–dimensional visual analogue scale score improved from baseline to Year 3 (70.1 vs 73.0; P=0.0045). Overall sustained improvement in physical, mental, and emotional aspects of QoL were observed through 3 years in this population of alemtuzumab-treated RRMS patients, even though most patients received only 2 alemtuzumab treatment courses.

MANAGEMENT OF ADVERSE REACTIONS TO ALEMTUZUMAB INFUSION

2015 ◽  
Vol 86 (11) ◽  
pp. e4.23-e4 ◽  
Author(s):  
Basil Sharrack ◽  
Lori Mayer ◽  
Alasdair Coles ◽  
Hans-Peter Hartung ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Symptomatic Treatment ◽  
Phase 3 ◽  
Prior Therapy ◽  
Link Type ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Relapsing Remitting Multiple Sclerosis

In the 2-year, phase 3 CARE-MS studies of alemtuzumab in patients with relapsing-remitting multiple sclerosis, infusion-associated reactions (IARs) were the most common adverse events. Here we report on IARs during 4-year follow-up. Patients who were treatment-naive (CARE-MS I; NCT00530348) or with inadequate efficacy response to prior therapy (CARE-MS II; NCT00548405) received 2 annual courses of alemtuzumab 12 mg, and as-needed retreatment in an extension study (NCT00930553). Patients received methylprednisolone on the first 3 days of each course. IARs were any adverse event occurring between start of infusion and within 24 hours after end of infusion. 742/811 alemtuzumab-treated patients entered extension. Over 4 years, 70.4% received only 2 initial treatment courses; 22.6% and 6.1% received 3 and 4 courses, respectively. IARs were most frequent in Course 1 (84.7%) versus Courses 2 (68.5%), 3 (65.7%), and 4 (71.1%); frequency decreased on infusion Days 2 and 3 versus Day 1. IARs were predominantly mild to moderate; none led to study withdrawal or death. Serious IAR incidence was 3.1%. Most common IARs were skin disorders (predominantly rash), headache, pyrexia, and nausea. One confirmed anaphylaxis and one non-anaphylactoid hypotension event resolved with treatment. Effective IAR management included premedication, infusion monitoring, symptomatic treatment, and infusion interruption/adjustment.

scholarly journals Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012700
Author(s):  
Stephen L Hauser ◽  
Ludwig Kappos ◽  
Xavier Montalban ◽  
Licinio Craveiro ◽  
Cathy Chognot ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Real World ◽  
Safety Profile ◽  
Progressive Multiple Sclerosis ◽  
Continuous Treatment ◽  
Primary Progressive Multiple Sclerosis ◽  
Class Iii ◽  
Primary Progressive ◽  
Controlled Treatment

ObjectiveTo report safety of ocrelizumab (OCR) up to 7 years in patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) enrolled in clinical trials or treated in real-world postmarketing settings.MethodsSafety analyses are based on integrated clinical and laboratory data for all patients who received OCR in 11 clinical trials, including the controlled treatment and open-label extension (OLE) periods of the phase 2 and 3 trials, plus the phase 3b trials VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, CONSONANCE, and LIBERTO. For selected adverse events (AEs), additional postmarketing data were used. Incidence rates of serious infections (SIs) and malignancies were contextualized using multiple epidemiologic sources.ResultsAt data cut-off (January 2020), 5,680 patients with multiple sclerosis (MS) received OCR (18,218 patient years [PY] of exposure) in clinical trials. Rates per 100 PY (95% CI) of AEs (248; 246–251), serious AEs (7.3; 7.0–7.7), infusion-related reactions (25.9; 25.1–26.6), and infections (76.2; 74.9–77.4) were similar to those within the controlled treatment period of the phase 3 trials. Rates of the most common serious AEs, including SIs (2.01; 1.81–2.23) and malignancies (0.46; 0.37–0.57), were consistent with the ranges reported in epidemiologic data.ConclusionContinuous administration of OCR for up to 7 years in clinical trials, as well as its broader use for more than 3 years in the real-world setting, are associated with a favorable and manageable safety profile, without emerging safety concerns in a heterogeneous MS population.Classification of evidenceThis analysis provides Class III evidence that long-term, continuous treatment with OCR has a consistent and favorable safety profile in patients with RMS and PPMS. This study is rated Class III because of the use of OLE data and historical controls.

044 Durable clinical efficacy of alemtuzumab in patients with active rrms in the absence of continuous treatment: 7-year follow-up of CARE-MS I patients (Topaz Study)

2018 ◽  
Vol 89 (6) ◽  
pp. A18.2-A19
Author(s):  
Pamela McCombe ◽  
Alexey N Boyko ◽  
Jérôme DeSeze ◽  
Hans-Peter Hartung ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Additional Treatment ◽  
Continuous Treatment ◽  
Link Type ◽  
Relapsing Remitting ◽  
Bayer Healthcare ◽  
Core Study ◽  
Treatment Naïve ◽  
Mri Scans ◽  
Study Support ◽  
Over Time

IntroductionIn CARE-MS I (NCT00530348), alemtuzumab 12 mg/day (baseline: 5 days; 12 months later: 3 days) improved clinical/MRI outcomes versus SC IFNB-1a over 2 years (y) in treatment-naive relapsing-remitting MS (RRMS) patients. Efficacy was durable in a 4-y extension (NCT00930553; 95% enrolled, 92% completed), wherein patients could receive as-needed alemtuzumab retreatment for relapse/MRI activity or other disease-modifying therapies (DMTs) per investigator’s discretion. Patients completing the extension could enrol in the 5-y TOPAZ study (NCT02255656) for further evaluation. Here we examine efficacy/safety through Y7 in alemtuzumab-treated patients from CARE-MS I.MethodsIn TOPAZ, patients can receive alemtuzumab retreatment (≥12 months apart) or other DMTs (both per investigator’s discretion). MRI scans are performed annually. Assessments: annualised relapse rate (ARR); stable/improved Expanded Disability Status Scale (EDSS) from core study baseline; 6 month confirmed disability worsening (CDW); 6 month confirmed disability improvement (CDI); no evidence of disease activity (NEDA); adverse events (AEs).Results299/321 patients (93%) completed TOPAZ Y1 (Y7 after initiating alemtuzumab). ARR remained low (Y7: 0.13); 60% were relapse-free in Y3–7. The percentage of patients with stable/improved EDSS remained high (Y7: 78%). Through Y7, 74% were free from 6 month CDW, 37% achieved 6 month CDI, and the majority achieved NEDA each year (Y7: 61%). 59% received no additional treatment (alemtuzumab or other DMT) after the initial 2 courses. Overall AE incidence, infusion-associated reactions, and infections decreased over time. Thyroid AE incidence peaked in Y3 (15%) and then declined.ConclusionAlemtuzumab efficacy was maintained for 7 years in treatment-naive patients, despite 59% receiving no additional treatment since the initial 2 courses. 37% of patients also showed disability improvement. The alemtuzumab safety profile remained consistent; overall AE incidence decreased over time. Alemtuzumab may provide a unique treatment approach for RRMS patients, offering durable efficacy in the absence of continuous treatment.Study supportSanofi and Bayer HealthCare Pharmaceuticals.

scholarly journals Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years

2021 ◽  
pp. annrheumdis-2021-221051
Author(s):  
Kevin L Winthrop ◽  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Alan Kivitz ◽  
Franziska Matzkies ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Link Type ◽  
Serious Infection ◽  
Grade 3 ◽  
Adjusted Incidence

ObjectiveTo characterise safety of the Janus kinase-1 preferential inhibitor filgotinib in patients with moderately to severely active rheumatoid arthritis.MethodsData were integrated from seven trials (NCT01668641, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700, NCT03025308). Results are from placebo (PBO)-controlled (through week (W)12) and long-term, as-treated (all available data for patients receiving ≥1 dose filgotinib 200 (FIL200) or 100 mg (FIL100) daily) datasets. We calculated exposure-adjusted incidence rates (EAIRs)/100 patient-years filgotinib exposure (100PYE) for treatment-emergent adverse events (TEAEs).Results3691 patients received filgotinib for 6080.7 PYE (median 1.6, maximum 5.6 years). During the PBO-controlled period, TEAEs, including those of grade ≥3, occurred at comparable rates with filgotinib or PBO; long-term EAIRs of TEAEs grade ≥3 were 6.4 and 7.6/100PYE for FIL200 and FIL100. EAIRs for deaths were 0.6/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.5 and 0.3/100PYE for FIL200 and FIL100. EAIRs for serious infection were 3.9, 3.3 and 2.4/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.6 and 3.1/100PYE for FIL200 and FIL100. EAIRs for herpes zoster were 0.6, 1.1, and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.8 and 1.1/100PYE for FIL200 and FIL100. EAIRs for major adverse cardiovascular events were 0, 1.7 and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.4 and 0.6/100PYE for FIL200 and FIL100. No venous thromboembolism occurred during the PBO-controlled period; long-term EAIRs were 0.2 and 0/100PYE for FIL200 and FIL100.ConclusionsOver a median of 1.6 and maximum of 5.6 years of exposure, safety/tolerability of FIL200 and FIL100 were similar, with a lower incidence of infections with FIL200 among the long-term, as-treated dataset.

Sign in / Sign up

Export Citation Format

Share Document