scholarly journals Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database

2021 ◽  
pp. annrheumdis-2021-221276
Author(s):  
Peter C Taylor ◽  
Tsutomu Takeuchi ◽  
Gerd R Burmester ◽  
Patrick Durez ◽  
Josef S Smolen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitor ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Phase Iii ◽  
Major Adverse Cardiovascular Events ◽  
Integrated Analysis ◽  
Link Type ◽  
Serious Infections

ObjectiveTo report long-term safety from the completed extension trial of baricitinib, an oral selective Janus kinase inhibitor, in patients with active rheumatoid arthritis (RA).MethodsTreatment-emergent adverse events are summarised from an integrated database (9 phase III/II/Ib and 1 long-term extension) of patients who received any baricitinib dose (All-bari-RA). Standardised incidence ratio (SIR) for malignancy (excluding non-melanoma skin cancer (NMSC)) and standardised mortality ratio (SMR) were estimated. Additional analysis was done in a subset of patients who had ever taken 2 mg or 4 mg baricitinib.Results3770 patients received baricitinib (14 744 patient-years of exposure (PYE)). All-bari-RA incidence rates (IRs) per 100 patient-years at risk were 2.6, 3.0 and 0.5 for serious infections, herpes zoster and major adverse cardiovascular events (MACE), respectively. In patients aged ≥50 with ≥1 cardiovascular risk factor, the IR for MACE was 0.77 (95% CI 0.56 to 1.04). The IR for malignancy (excluding NMSC) during the first 48 weeks was 0.6 and remained stable thereafter (IR 1.0). The SIR for malignancies excluding NMSC was 1.07 (95% CI 0.90 to 1.26) and the SMR was 0.74 (95% CI 0.59 to 0.92). All-bari-RA IRs for deep vein thrombosis (DVT)/pulmonary embolism (PE), DVT and PE were 0.5 (95% CI 0.38 to 0.61), 0.4 (95% CI 0.26 to 0.45) and 0.3 (95% CI 0.18 to 0.35), respectively. No clear dose differences were noted for exposure-adjusted IRs (per 100 PYE) for deaths, serious infections, DVT/PE and MACE.ConclusionsIn this integrated analysis including long-term data of baricitinib from 3770 patients (median 4.6 years, up to 9.3 years) with active RA, baricitinib maintained a similar safety profile to earlier analyses. No new safety signals were identified.Trial registration numberNCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT02265705, NCT01721044, NCT01721057, NCT01711359 and NCT01885078.

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.

scholarly journals Oral Janus Kinase Inhibitor for the Treatment of Rheumatoid Arthritis: Tofacitinib

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Han Ni ◽  
Soe Moe ◽  
Kay Thi Myint ◽  
Aung Htet
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Profile ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Serious Adverse Events ◽  
Janus Kinase Inhibitor ◽  
Immune Modulators ◽  
Serious Infections

Since the introduction of immune modulators in the treatment of rheumatoid arthritis (RA), there has been hope that orally effective biologic agents would be developed. Tofacitinib, a Janus kinase inhibitor, has become the first oral biologic to receive approval for use in active RA patients. This paper reviews the efficacy and safety profile of Tofacitinib at dosages of 5 mg and 10 mg twice daily. Remarkable improvement in terms of ACR 20 response and HAQ-DI score was noted at month 3 and month 6. DAS 28-4 ESR < 2.6 achievement was noticeably obvious at month 6 for both dosages. No significant serious adverse events, serious infections, neutropenia, or anaemia were observed compared to placebo. In fact, Tofacitinib 5 mg was even found to have significant protective effect of anaemia in the meta-analysis (P=0.004). Tofacitinib has a noticeable efficacy in controlling disease activity in RA with a manageable safety profile. However, longer studies are needed for its long-term safety profile.

scholarly journals Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment

2018 ◽  
Vol 46 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Josef S. Smolen ◽  
Mark C. Genovese ◽  
Tsutomu Takeuchi ◽  
David L. Hyslop ◽  
William L. Macias ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Profile ◽  
Active Rheumatoid Arthritis ◽  
Prolonged Exposure ◽  
Janus Kinase ◽  
Phase Iii ◽  
Integrated Analysis ◽  
Drug Discontinuation ◽  
Adverse Cardiovascular Event ◽  
Link Type

Objective.Baricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA). We evaluated baricitinib’s safety profile through 288 weeks (up to September 1, 2016) with an integrated database [8 phase III/II/Ib trials, 1 longterm extension (LTE)].Methods.The “all-bari-RA” group included patients who received any baricitinib dose. Placebo comparison was based on the 6 studies with 4 mg and placebo up to Week 24 (“placebo-4 mg” dataset). Dose response assessment was based on 4 studies with 2 mg and 4 mg including LTE data (“2 mg-4 mg–extended”). The uncommon events description used the non-controlled all-bari-RA.Results.There were 3492 patients who received baricitinib for 6637 total patient-years (PY) of exposure (median 2.1 yrs, maximum 5.5 yrs). No differences in rates of death, adverse events leading to drug discontinuation, malignancies, major adverse cardiovascular event (MACE), or serious infections were seen for 4 mg versus placebo or for 4 mg versus 2 mg. Infections including herpes zoster were significantly more frequent for 4 mg versus placebo. Deep vein thrombosis/pulmonary embolism were reported with 4 mg but not placebo [all-bari-RA incidence rate (IR) 0.5/100 PY]; the IR did not differ between doses (0.5 vs 0.6/100 PY, 2 mg vs 4 mg, respectively) or compared to published RA rates. All-bari-RA had 6 cases of lymphoma (IR 0.09/100 PY), 3 gastrointestinal perforations (0.05/100 PY), 10 cases of tuberculosis (all in endemic areas; 0.15/100 PY), and 22 all-cause deaths (0.33/100 PY). IR for malignancies (0.8/100 PY) and MACE (0.5/100 PY) were low and did not increase with prolonged exposure.Conclusion.In this integrated analysis of patients with moderate to severe active RA with exposure up to 5.5 years, baricitinib has an acceptable safety profile in the context of demonstrated efficacy. Trial registration numbers:NCT01185353,NCT00902486,NCT01469013,NCT01710358,NCT01721044,NCT01721057,NCT01711359, andNCT01885078atclinicaltrials.gov.

scholarly journals Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme

2020 ◽  
pp. annrheumdis-2020-218510 ◽  
Author(s):  
Stanley B Cohen ◽  
Ronald F van Vollenhoven ◽  
Kevin L Winthrop ◽  
Cristiano A F Zerbini ◽  
Yoshiya Tanaka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Herpes Zoster ◽  
Tract Infection ◽  
Safety Profile ◽  
Janus Kinase ◽  
Phase Iii ◽  
Integrated Analysis ◽  
Upper Respiratory Tract ◽  
Link Type ◽  
Venous Thromboembolic Events

ObjectivesThis integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA).MethodsTreatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or active-controlled phase III trials of upadacitinib for patients with RA were analysed and summarised. Exposure-adjusted event rates are shown for placebo (three trials; 12/14 weeks), methotrexate (two trials; mean exposure: 36 weeks), adalimumab (one trial; mean exposure: 42 weeks), upadacitinib 15 mg (five trials; mean exposure: 53 weeks) and upadacitinib 30 mg (four trials; mean exposure: 59 weeks).Results3834 patients received one or more doses of upadacitinib 15 mg (n=2630) or 30 mg (n=1204), for a total of 4020.1 patient-years of exposure. Upper respiratory tract infection, nasopharyngitis and urinary tract infection were the most commonly reported TEAEs with upadacitinib. Rates of serious infection were similar between upadacitinib 15 mg and adalimumab but higher compared with methotrexate. Rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both upadacitinib groups versus methotrexate and adalimumab, and rates of gastrointestinal perforations were higher with upadacitinib 30 mg. Rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) were similar across treatment groups.ConclusionIn the phase III clinical programme for RA, patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab. Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab.Trial registration numbersSELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847.

scholarly journals Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme

RMD Open ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e001395 ◽  
Author(s):  
Stanley B Cohen ◽  
Yoshiya Tanaka ◽  
Xavier Mariette ◽  
Jeffrey R Curtis ◽  
Eun Bong Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Phase I ◽  
Safety Analysis ◽  
Development Programme ◽  
Clinical Development ◽  
Janus Kinase ◽  
Phase Iii ◽  
Jak Inhibitor ◽  
Link Type

ObjectiveTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). We report the largest integrated safety analysis of tofacitinib, as of March 2017, using data from phase I, II, III, IIIb/IV and long-term extension studies in adult patients with RA.MethodsData were pooled for patients with RA who received ≥1 tofacitinib dose. Incidence rates (IRs; patients with events/100 patient-years [PY]; 95% CIs) of first-time occurrences were obtained for adverse events (AEs) of interest.Results7061 patients received tofacitinib (total exposure: 22 875 PY; median [range] exposure: 3.1 [0 to 9.6] years). IRs (95% CI) for serious AEs, serious infections, herpes zoster (all), opportunistic infections (excluding tuberculosis [TB]) and TB were 9.0 (8.6 to 9.4), 2.5 (2.3 to 2.7), 3.6 (3.4 to 3.9), 0.4 (0.3 to 0.5) and 0.2 (0.1 to 0.2), respectively. IRs (95% CI) for malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC and lymphomas were 0.8 (0.7 to 0.9), 0.6 (0.5 to 0.7) and 0.1 (0.0 to 0.1), respectively. IRs (95% CI) for gastrointestinal perforations, deep vein thrombosis, pulmonary embolism, venous thromboembolism, arterial thromboembolism and major adverse cardiovascular events were 0.1 (0.1 to 0.2), 0.2 (0.1 to 0.2), 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.3), 0.4 (0.3 to 0.5) and 0.4 (0.3 to 0.5), respectively. IR (95% CI) for mortality was 0.3 (0.2 to 0.3). IRs generally remained consistent across 6-month intervals to >78 months.ConclusionThis represents the largest clinical dataset for a JAK inhibitor in RA to date. IRs remained consistent with previous reports from the tofacitinib RA clinical development programme, and stable over time.Trial registration numbersNCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661.For summary of phase I, phase II, phase III, phase IIIb/IV and LTE studies included in the integrated safety analysis, see online supplemental table 1.

scholarly journals P220 An updated safety profile of baricitinib for the treatment of RA up to 7 years

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
David Walker ◽  
Ilias Kouris ◽  
Thorsten Holzkämper ◽  
Marco W Wu ◽  
Ricardo Xavier ◽  
...  
Keyword(s):  
Safety Profile ◽  
Opportunistic Infections ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Integrated Analysis ◽  
Data Set ◽  
Serious Infections ◽  
Geographical Regions ◽  
Over Time

Abstract Background Baricitinib (BARI) is a selective inhibitor of janus kinase (JAK) 1 and JAK2, approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults in over 50 countries. Objective: To evaluate the long-term safety of BARI in patients with RA with a specific focus on malignancies, major adverse cardiovascular events (MACE), serious infections and herpes zoster (HZ) events. Methods Data from nine completed studies (5 Phase 3, 3 Phase 2, 1 Phase 1b) and 1 long term extension (LTE) study were pooled for this analysis (data cut-off date: 13-Feb-2018). The all BARI data set included all patients exposed to any BARI dose. Results A total of 3,770 patients with RA were treated with BARI (10,127 patient years [PY]) with a maximum exposure of 7 years. Of these, 2,938 (78%) and 1,754 (47%) were on concomitant methotrexate or corticosteroids (CS; mean dose 6.2 mg/day), respectively. The incidence rates (IR) of malignancy (excluding non-melanoma skin cancer) were 0.8 (2-mg) and 1.0 (4-mg; as-randomized analysis) in the LTE. The IRs for MACE were similar between the all BARI and PBO group; however, the IR for DVT/PE were numerically higher in the BARI 4mg group during the PBO-controlled period. IRs for MACE remain stable over time. The IR of serious infections were numerically higher in the PBO group; the IR of tuberculosis and other opportunistic infections were similar between the all BARI and PBO group. During the PBO-controlled period, HZ IR was significantly higher for BARI 4-mg versus PBO (4.4 vs 1.1) (Table 1). Amongst 323 HZ patients, 11 (4%) had received prior HZ vaccination. Twenty-six [8%] cases were multidermatomal, and no visceral disease was reported. Multivariate analyses showed that older age and some geographical regions (Asia, especially Japan, Taiwan and South Korea) were associated with a higher risk of HZ. Conclusion This integrated analysis in patients with active RA exposed to BARI for up to 7 years shows that the safety profile of BARI is like that reported previously. The IRs of malignancies, MACE (including DVT/PE), serious infection, and HZ did not increase over time. Disclosures D. Walker: Honoraria; Lilly, Pfizer, Giliad, Novartis, Roche. Member of speakers’ bureau; Lilly, Pfizer, Roche. I. Kouris: Other; Lilly employee. T. Holzkämper: Shareholder/stock ownership; Lilly. Other; Lilly employee. M.W. Wu: Other; Lilly employee. R. Xavier: None. J. Smolen: Consultancies; Abbvie, Amgen, Astra Zeneca, Astro, BMS. Grants/research support; Abbvie, Eli Lilly, Novartis, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB. P. Durez: Member of speakers’ bureau; Abbvie, BMS, Celltrion, Eli Lilly. Y. Chen: None. J. Zhong: Corporate appointments; Eli Lilly Contractor. R. Liao: Other; Lilly employee. M.C. Genovese: Consultancies; Eli Lilly. K. Winthrop: Consultancies; Pfizer, UCB, Eli Lilly, Gilead, Abbvie, Roche, BMS.

scholarly journals Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up

Rheumatology ◽  
2019 ◽  
Vol 59 (2) ◽  
pp. 292-302 ◽  
Author(s):  
Roy Fleischmann ◽  
Mark C Genovese ◽  
Yong Lin ◽  
Gregory St John ◽  
Désirée van der Heijde ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Group Treatment ◽  
Human Monoclonal Antibody ◽  
Incidence Rates ◽  
Major Adverse Cardiovascular Events ◽  
Combination Group ◽  
Integrated Analysis ◽  
Open Label ◽  
Increased Risk

Abstract Objective Sarilumab is a human monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor-α. We assessed the long-term safety of sarilumab in patients from eight clinical trials and their open-label extensions. Methods Data were pooled from patients with rheumatoid arthritis who received at least one dose of sarilumab in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and AEs and laboratory values of special interest were assessed. Results 2887 patients received sarilumab in combination with csDMARDs and 471 patients received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 and 812 patient-years, respectively. Incidence rates per 100 patient-years in the combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute neutrophil counts &lt;1000 cells/mm3 were recorded in 13% and 15% of patients, respectively. Neutropenia was not associated with increased risk of infection or serious infection. Analysis by 6-month interval showed no signal for increased rate of any AE over time. Conclusion The long-term safety profile of sarilumab, either in combination with csDMARDs or as monotherapy, remained stable and consistent with the anticipated profile of a molecule that inhibits IL6 signalling.

scholarly journals DOP61 Tofacitinib, an oral, small-molecule Janus kinase inhibitor, in the treatment of ulcerative colitis: Analysis of an open-label, long-term extension study with up to 5.9 years of treatment

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S100-S101 ◽  
Author(s):  
G R Lichtenstein ◽  
E V Loftus ◽  
S C Wei ◽  
A O Damião ◽  
D Judd ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Small Molecule ◽  
Kinase Inhibitor ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Open Label ◽  
Mayo Score

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were demonstrated in patients with moderate to severe UC in 3 Phase 3 studies.1 Here, we present data from an ongoing, open-label, long-term extension (OLE) study.2 Methods We present updated safety and efficacy data from the OLE study (OCTAVE Open, NCT01470612; as of May 2019, database not locked). Eligible patients included non-responders (Week 8 data) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951) and completers (Week 52 data) or treatment failures (early-termination data) in OCTAVE Sustain (NCT01458574). Patients in remission (total Mayo score ≤2, no individual subscore &gt;1, rectal bleeding [RB] subscore 0) at Week 52 of OCTAVE Sustain (central read) received tofacitinib 5 mg twice daily (BID); all others received 10 mg BID. Induction non-responders without clinical response (≥3-point and ≥30% decrease from induction study baseline total Mayo score, plus ≥1-point RB subscore decrease or absolute RB subscore ≤1) at Month 2 of the OLE study were withdrawn. Incidence rates (IRs) for adverse events (AEs) of special interest were calculated (no. of unique patients with events per 100 patient-years). Efficacy endpoints were derived from Mayo score (local read) with non-responder and last observation carried forward imputation (NRI-LOCF) [a]. Results Of 944 patients who received ≥1 dose of tofacitinib, 769 (81.5%) received 10 mg BID (median duration [range]: 5 mg BID 1170 [36–2066]; 10 mg BID 668 [1–2159] days). In total, 338 (35.8%) and 93 (9.9%) patients discontinued due to insufficient clinical response and AEs (excl. worsening UC), respectively. IRs (95% confidence interval) in the Tofacitinib. All group were: deaths 0.18 (0.05, 0.47); serious infections 1.57 (1.08, 2.19); herpes zoster (non-serious and serious) 3.27 (2.54, 4.14); major adverse cardiovascular events 0.14 (0.03, 0.40); malignancies excl. non-melanoma skin cancer (NMSC) 0.92 (0.56, 1.42); NMSC 0.74 (0.43, 1.21); deep vein thrombosis 0.05 (0.00, 0.25); pulmonary embolism 0.18 (0.05, 0.47) (Table). At Month 36 (NRI-LOCF), 58.9% (n = 103) and 33.5% (n = 257) were in remission, 64.6% (n = 113) and 37.0% (n = 284) had mucosal healing (Mayo endoscopic subscore of 0 or 1) [b] and 66.9% (n = 117) and 40.2% (n = 309) showed clinical response, in the 5 and 10 mg BID groups, respectively. Conclusion Incidence of AEs remained generally consistent in patients with moderate to severe UC in the OLE study compared with a previous analysis.2 Data continue to support long-term efficacy with tofacitinib up to 36 months beyond Week 52 of OCTAVE Sustain. References

scholarly journals O09 Safety profile of baricitinib for the treatment of RA up to 8.4 years: an updated integrated safety analysis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Kevin L Winthrop ◽  
Tsutomu Takeuchi ◽  
Gerd Burmester ◽  
Walter Deberdt ◽  
Douglas Schlichting ◽  
...  
Keyword(s):  
Safety Profile ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Stock Ownership ◽  
Research Support ◽  
Vein Thrombosis ◽  
Non Melanoma Skin Cancer ◽  
Deep Vein

Abstract Background/Aims  Baricitinib (BARI) is an oral selective inhibitor of Janus kinase (JAK)1/2, approved for treatment of moderate-to-severe- rheumatoid arthritis (RA) in adults. Here, we update the drug’s safety profile with data up to 8.4 years of treatment. Methods  Long-term safety of BARI was assessed from 9 completed randomized trials(5 Ph3, 3 Ph2, 1 Ph 1b) and 1 ongoing long-term extension(LTE) study. Incidence rates(IRs) per 100 patient-years (PY) were calculated for all RA patients treated with ≥1 dose of BARI through 1-Sep-2019(All-BARI-RA set). IRs for deep vein thrombosis(DVT), pulmonary embolism(PE), and DVT and/or PE(DVT/PE) were also calculated for groups of patients while receiving BARI 2mg/4mg within All-BARI-RA. Major adverse cardiovascular events(MACE) were adjudicated in 5 Ph3 studies and the LTE. Results  3770 pts received BARI for 13,148 PY, with median and maximum exposure: 4.2 and 8.4 years, respectively. Overall IRs per 100 PY were: for any treatment-emergent adverse event (AE)(25.8); serious AE (including death)(7.2); temporary interruption due to AE (9.5); permanent discontinuation due to AE (4.8); death (0.52); serious infection (2.7); opportunistic infection (0.46)(excluding tuberculosis [TB], including multidermatomal herpes zoster [HZ]); TB (0.15); HZ (3.0); MACE (0.50); DVT (0.31); PE (0.24); DVT/PE (0.46); malignancies excluding non-melanoma skin cancer (NMSC)(0.91); NMSC (0.33); lymphoma (0.07); and gastrointestinal perforation (0.04). (IRs)[95% confidence intervals] for patients while receiving BARI 2mg (N = 1077) and BARI 4mg (N = 3400) were DVT 2mg (0.38)[0.18, 0.73] and 4mg (0.30)[0.21, 0.43]; PE 2mg (0.26)[0.09, 0.56] and 4mg (0.25)[0.16, 0.36]; and DVT/PE 2mg (0.47)[0.23, 0.84] and 4mg (0.46)[0.34, 0.61]. IRs for death tended to increase in later time intervals (beyond 192 weeks). No particular cause of death contributed to this increase. For all other safety topics of interest, across 48-week treatment intervals, IRs remained stable over time. Across safety topics, IRs were consistent with previous analyses. Conclusion  In this update, with 3021 additional PY of exposure, BARI maintained a safety profile similar to that previously reported, with no increase of IRs across safety topics through exposures up to 8.4 years. Disclosure  K.L. Winthrop: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and UCB Pharma. Grants/research support; Bristol Myers Squibb and Pfizer. T. Takeuchi: Consultancies; AbbVie, Asahi Kasei Medical, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis, Pfizer Japan, Taiho Pharmaceutical, Taiho Toyama Pharmaceutical, Takeda, and UCB Japan. G. Burmester: Consultancies; Eli Lilly and Company, Janssen, Novartis, and Pfizer. Grants/research support; Eli Lilly and Company. W. Deberdt: Shareholder/stock ownership; Eli Lilly and Company. D. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. D. Mo: Shareholder/stock ownership; Eli Lilly and Company. C. Walls: Shareholder/stock ownership; Eli Lilly and Company. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro Pharma, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Eli Lilly and Company, Gilead Sciences, ILTOO Pharma, Janssen, MedImmune, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB Pharma. Grants/research support; AbbVie, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.

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