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

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.

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-221276 ◽

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.

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

Rheumatology ◽

10.1093/rheumatology/keab246.008 ◽

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

ISRN Rheumatology ◽

10.1155/2013/357904 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 5

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.

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Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials

Rheumatology ◽

10.1093/rheumatology/keaa189 ◽

2020 ◽

Vol 59 (12) ◽

pp. 3834-3844 ◽

Cited By ~ 3

Author(s):

Mark C Genovese ◽

Eduardo Mysler ◽

Tetsuya Tomita ◽

Kim A Papp ◽

Carlo Salvarani ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Injection Site ◽

Safety Profile ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Integrated Analysis ◽

Entire Treatment Period ◽

Injection Site Reactions

Abstract Objectives The aim of this integrated analysis is to evaluate the long-term safety and tolerability of ixekizumab in adults with psoriasis, PsA and axial SpA. Methods Integrated safety data from 21 clinical trials are presented by indication in patients who received at least one dose of ixekizumab. Adverse events (AEs) and treatment-emergent adverse events (TEAEs) adjusted incidence rates (IRs) per 100 patient-years (PY) up to 5 years’ exposure are reported. Results A total of 8228 patients with an ixekizumab exposure of 20 895.9 PY were included in this analysis. The most common TEAEs were nasopharyngitis, upper respiratory tract infection and injection-site reactions. Across populations, IRs were low for AEs leading to discontinuation (IRs ≤5.1 per 100 PY), serious AEs (IRs ≤6.0 per 100 PY) and death (IRs ≤0.3 per 100 PY). The most reported TEAEs of special interest were infections (IRs ≤35.8 per 100 PY). Patients rarely reported malignancies (IR ≤0.8), IBD including ulcerative colitis and Crohn’s disease (IR ≤0.8) and major adverse cardiovascular events (IR ≤0.5). TEAEs were most commonly reported the first 2 years of exposure with ixekizumab and IR decreased over the years (infections, injection-site reactions and depression) or remained constant over the entire treatment period (serious infections, major adverse cardiovascular events, malignancies and IBD). Conclusion This long-term analysis on the safety of ixekizumab was consistent with previously published reports and did not show any new safety signals. The safety profile and tolerability reported in this integrated analysis remained consistent with the known safety profile for ixekizumab.

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Investigating the Broken-Heart Effect: a Model for Short-Term Dependence between the Remaining Lifetimes of Joint Lives

Annals of Actuarial Science ◽

10.1017/s1748499512000292 ◽

2012 ◽

Vol 7 (2) ◽

pp. 236-257 ◽

Cited By ~ 12

Author(s):

Jaap Spreeuw ◽

Iqbal Owadally

Keyword(s):

Mortality Rates ◽

Short Term ◽

Numerical Work ◽

Data Set ◽

Multiple State ◽

Multiple State Model ◽

Insurance Data ◽

Over Time ◽

Assurance Contracts

AbstractWe analyze the mortality of couples by fitting a multiple state model to a large insurance data set. We find evidence that mortality rates increase after the death of a partner and, in addition, that this phenomenon diminishes over time. This is popularly known as a “broken-heart” effect and we find that it affects widowers more than widows. Remaining lifetimes of joint lives therefore exhibit short-term dependence. We carry out numerical work involving the pricing and valuation of typical contingent assurance contracts and of a joint life and survivor annuity. If insurers ignore dependence, or mis-specify it as long-term dependence, then significant mis-pricing and inappropriate provisioning can result. Detailed numerical results are presented.

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Two decades of in-situ temperature measurements in the upper troposphere and lowermost stratosphere from IAGOS long-term routine observation

10.5194/acp-2017-494 ◽

2017 ◽

Author(s):

Florian Berkes ◽

Patrick Neis ◽

Martin G. Schultz ◽

Ulrich Bundke ◽

Susanne Rohs ◽

...

Keyword(s):

Weather Forecast ◽

Global Scale ◽

Temperature Trend ◽

Data Set ◽

Medium Range Weather Forecast ◽

Upper Troposphere ◽

Temperature Trends ◽

Geographical Regions

Abstract. Despite several studies on temperature trends in the tropopause region, a comprehensive understanding of the evolution of temperatures in this climate-sensitive region of the atmosphere remains elusive. Here we present a unique global-scale, long-term data set of high-resolution in-situ temperature data measured aboard passenger aircraft within the European Research Infrastructure IAGOS (In-service Aircraft for a Global Observing System, www.iagos.org). This data set is used to investigate temperature trends within the global upper troposphere and lowermost stratosphere (UTLS) for the period 1995 to 2012 in different geographical regions and vertical layers of the UTLS. The largest amount of observations is available over the North Atlantic. Here, a neutral temperature trend is found within the lowermost stratosphere. This contradicts the temperature trend in the European Centre for Medium Range Weather Forecast (ECMWF) ERA-Interim reanalysis, where a significant (95 % confidence) temperature increase of +0.56 K/decade is obtained. Differences between trends derived from observations and reanalysis data can be traced back to changes in the temperature bias between observation and model data over the studied period. This study demonstrates the value of the IAGOS temperature observations as anchor point for the evaluation of reanalyses and its suitability for independent trend analyses.

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Long-Term Safety Profile of the Oral Spleen Tyrosine Kinase Inhibitor Fostamatinib in Immune Thrombocytopenia (ITP) and Other Diseases

Blood ◽

10.1182/blood-2020-140907 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 35-36

Author(s):

Sandra Tong ◽

Robert P. Numerof ◽

Jane Datangel ◽

Esteban Masuda

Keyword(s):

Tyrosine Kinase ◽

Safety Profile ◽

Safety Data ◽

First Year ◽

Patient Exposure ◽

Publicly Traded ◽

Data Set ◽

Pooled Data ◽

The Mean

Introduction: Fostamatinib is an oral, potent inhibitor of spleen tyrosine kinase (SYK) with proven efficacy and a manageable safety profile for the treatment of ITP. SYK is situated in an intracellular signaling pathway upstream of Bruton's tyrosine kinase (BTK). Long-term safety data on fostamatinib at various dosing regimens (up to 150 mg BID) has been collected in >4000 patients with ITP, rheumatoid arthritis (RA), and other autoimmune, allergic and neoplastic disorders. The safety and tolerability of fostamatinib were consistent across different patient populations (apart from disease specific events). We present a summary analysis of the fostamatinib safety data from the ITP and RA studies. Methods: Fostamatinib safety data from 2 randomized, double-blind, placebo-controlled, phase 3 studies and the long-term, open-label, extension (OLE) study in ITP were pooled and are based on a starting dose of 200 mg/day, which was increased to 300 mg/day after 4 weeks in 88% of patients. Fostamatinib safety data from 13 phase 2/3 studies in RA were pooled and are based on a dosing regimen of 100-150 mg/day (n=1232) or 200-300 mg/day (n=2205). Results: The pooled data set for ITP included 146 patients; 60% were female, and the median age was 53 years (range 20-88). The mean duration of fostamatinib treatment was 19 months (range <1-62 months), representing 229 patient exposure years. Adverse events (AEs) were reported in 87% of patients, and 63% were mild to moderate. Serious AEs were reported in 31% of patients. The incidence of diarrhea, hypertension, alanine aminotransferase increase (ALT), and aspartate aminotransferase (AST) increase was evaluated in 58 patients who received fostamatinib for ≥1 year. This enabled a comparison of the incidence of these AEs in quartiles over the first year to assess the cumulative effects of fostamatinib. The AEs were reported with decreasing frequency during the second, third, and fourth quarters of fostamatinib treatment compared with the first quarter of the initial year of treatment in the 58 patients (see Figure 1). In the same 58 patients, the use of rescue therapy decreased while median platelet counts increased each quarter of the first year. The pooled data set for RA included 3437 patients who received fostamatinib; 83% were female, and the median age was 54 (range 18 -87). The mean duration of treatment was 18 months (range <1-81) representing 5134 patient exposure years. AEs were reported in 86% of RA patients and were mild to moderate in 73% of RA patients. Serious AEs occurred in 14%. In the placebo-controlled RA studies, 2414 patients received fostamatinib with 823 patient exposure years and 1169 received placebo with 367 patient exposure years. Despite a two-fold (125%) increase in exposure with fostamatinib vs placebo (823 vs 367 patient exposure years), there was only a 26% increase in AEs with fostamatinib vs placebo (68% vs 54%). The most common events in the ITP and RA studies were diarrhea (36% and 24%), hypertension (22% and 19%) and nausea (19% and 8%), apart from disease-related AEs. Epistaxis (19% and 0.5%), petechiae (15% and 0.3%), contusion (12% and 2%), and fatigue (10% and 2%) are associated with ITP and were uncommon in the RA population. Rheumatoid arthritis was reported as an AE in 9% of patients with RA and in none with ITP. Some AEs may be dose-related, and one-third of the RA patients were on lower dosages (100-150 mg/day) than were generally given in the ITP trials (200-300 mg/day). Conclusions: Fostamatinib has been evaluated in >4000 patients across different disease populations. Fostamatinib has a consistent and manageable safety profile. No new safety signals and no cumulative toxicity were observed with up to 81 months (6.8 years) of continuous treatment. Figure 1 Disclosures Tong: Rigel: Current Employment, Current equity holder in publicly-traded company. Numerof:Rigel: Current Employment, Current equity holder in publicly-traded company. Datangel:Rigel: Current Employment, Current equity holder in publicly-traded company. Masuda:Rigel: Current Employment, Current equity holder in publicly-traded company.

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

The Journal of Rheumatology ◽

10.3899/jrheum.171361 ◽

2018 ◽

Vol 46 (1) ◽

pp. 7-18 ◽

Cited By ~ 85

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.

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DOP59 Maintenance of remission with tofacitinib in patients with ulcerative colitis: Updated results of a subpopulation analysis from an open-label, long-term extension study, OCTAVE Open

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.098 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S098-S099

Author(s):

J F Colombel ◽

M T Osterman ◽

P Ibanez ◽

A J Thorpe ◽

H Zhang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Opportunistic Infections ◽

Safety Data ◽

Similar Efficacy ◽

Major Adverse Cardiovascular Events ◽

Open Label ◽

Phase 3 ◽

Vein Thrombosis ◽

Mayo Score

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety were demonstrated in 3 Phase 3, randomised, placebo-controlled studies in patients with moderate to severe UC.1 An ongoing, Phase 3, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) included patients from OCTAVE Induction 1 and 2 and OCTAVE Sustain. Methods We present data (as of May 2019) from the ‘maintenance remission’ subpopulation in the OLE study who were in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore of 0) at Week 52 of OCTAVE Sustain (having received tofacitinib 5 or 10 mg twice daily [BID]). These patients received tofacitinib 5 mg BID as per protocol in the OLE study. Efficacy data up to Month 36 of the OLE study (as observed and with non-responder and last observation carried forward imputation [NRI-LOCF]) are presented for this subpopulation. Safety data are reported for all patients who received tofacitinib 5 mg BID in the OLE study. Results Of 944 patients receiving ≥1 dose of tofacitinib in the OLE study, 163 were in remission at Week 52 of OCTAVE Sustain (mean age 45 years; 46.0% female). Of these, 66 (40.5%) and 76 (46.6%) received tofacitinib 5 and 10 mg BID, respectively, in OCTAVE Sustain, and 21 (12.9%) received a placebo. In total, 67/163 (41.1%) patients discontinued the OLE study, 16 (9.8%) due to adverse events (AEs) excl. worsening UC and 15 (9.2%) due to insufficient clinical response. Among patients that continued, efficacy (Table) was maintained over 36 months and was similar irrespective of the dose received in OCTAVE Sustain. Of 175 patients who received tofacitinib 5 mg BID (incl. 163 from the maintenance remission subpopulation), 152 (86.9%), 33 (18.9%) and 20 (11.4%) had AEs, serious AEs and severe AEs, respectively. The most frequent treatment-emergent AEs (TEAEs) were worsening UC (41 patients, 23.4%) and nasopharyngitis (38 patients, 21.7%). Six (3.4%) patients receiving tofacitinib 5 mg BID had serious infections, 11 (6.3%) had herpes zoster (non-serious and serious), 4 (2.3%) had opportunistic infections, 2 (1.1%) had major adverse cardiovascular events and 5 (2.9%) had malignancy (excl. non-melanoma skin cancer). No deep vein thrombosis, pulmonary embolism or deaths were reported in patients receiving tofacitinib 5 mg BID. Conclusion Most patients in remission at Week 52 of OCTAVE Sustain maintained efficacy with tofacitinib 5 mg BID over 36 months in the OLE study. Similar efficacy was observed for patients whose dose was reduced from tofacitinib 10 mg BID in OCTAVE Sustain to 5 mg BID in the OLE study, vs. those who received 5 mg BID throughout both OCTAVE Sustain and the OLE study. No new safety risks were identified. Reference

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Upper tropospheric water vapour and its interaction with cirrus clouds as seen from IAGOS long-term routine in situ observations

Faraday Discussions ◽

10.1039/c7fd00006e ◽

2017 ◽

Vol 200 ◽

pp. 229-249 ◽

Cited By ~ 7

Author(s):

Andreas Petzold ◽

Martina Krämer ◽

Patrick Neis ◽

Christian Rolf ◽

Susanne Rohs ◽

...

Keyword(s):

Water Vapour ◽

Dynamic Equilibrium ◽

North Atlantic Ocean ◽

Global Scale ◽

Data Set ◽

Geographical Regions ◽

Tropopause Region ◽

Passenger Aircraft

IAGOS (In-service Aircraft for a Global Observing System) performs long-term routinein situobservations of atmospheric chemical composition (O3, CO, NOx, NOy, CO2, CH4), water vapour, aerosols, clouds, and temperature on a global scale by operating compact instruments on board of passenger aircraft. The unique characteristics of the IAGOS data set originate from the global scale sampling on air traffic routes with similar instrumentation such that the observations are truly comparable and well suited for atmospheric research on a statistical basis. Here, we present the analysis of 15 months of simultaneous observations of relative humidity with respect to ice (RHice) and ice crystal number concentration in cirrus (Nice) from July 2014 to October 2015. The joint data set of 360 hours of RHice–Niceobservations in the global upper troposphere and tropopause region is analysed with respect to the in-cloud distribution of RHiceand related cirrus properties. The majority of the observed cirrus is thin withNice< 0.1 cm−3. The respective fractions of all cloud observations range from 90% over the mid-latitude North Atlantic Ocean and the Eurasian Continent to 67% over the subtropical and tropical Pacific Ocean. The in-cloud RHicedistributions do not depend on the geographical region of sampling. Types of cirrus origin (in situorigin, liquid origin) are inferred for differentNiceregimes and geographical regions. Most importantly, we found that in-cloud RHiceshows a strong correlation toNicewith slightly supersaturated dynamic equilibrium RHiceassociated with higherNicevalues in stronger updrafts.

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