Fri0123 safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis Up to 8.4 Years: An Updated Integrated Safety Analysis

Genovese, M. C.; Smolen, JS; Takeuchi, T.; Burmester, G. R.; Deberdt, Walter; Schlichting, D.; Song, H.; Mo, Dan; Walls, Chad D.; Winthrop, K.L.

doi:10.1136/annrheumdis-2020-eular.1723

Cited by 14 publications

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“…4-18 23 26 Rates of SIEs previously reported in tofacitinib-treated patients with RA were generally comparable with those for patients treated with bDMARDs, baricitinib and upadacitinib. [27][28][29][30][31] In this analysis, the most common types of SIEs were pneumonia, HZ, urinary tract infection and cellulitis, which is consistent with the prior analysis 23 and those reported for baricitinib and upadacitinib. 27 32 Notably, there was an increased risk of SIEs with lymphopenia <500 cells/µL (HR 2.4), which was observed previously, 23 and also with lymphopenia <1000 cells/µL (HR 1.3).…”

Section: Discussionsupporting

confidence: 82%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 82%

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

et al. 2020

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“…During the placebocontrolled portion of the phase III studies, there was an imbalance in the development of VTEs, which occurred only in the 4 mg group and not in the 2 mg or placebo groups. However, in a report of >8 years of follow-up, the incidence rate of VTE was comparable between the 2 mg and 4 mg groups and similar to what has been observed in RA patients treated with agents with other mechanisms of action (46). No disparity was seen in the clinical trials of tofacitinib (34) and upadacitinib (55).…”

Section: Safety Of Approved Jakinibssupporting

confidence: 71%

“…Many of the AEs seen with jakinibs could have been predicted based on their mechanism of action, while others could not. Common side effects are infections, including serious and opportunistic infections and herpes zoster (45)(46)(47). Vaccination with recombinant adjuvanted herpes zoster subunit is generally safe in patients with autoimmune disease, although flares are not uncommon (48,49).…”

Section: Safety Of Approved Jakinibsmentioning

confidence: 99%

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A Decade of JAK Inhibitors: What Have We Learned and What May Be the Future?

Liu

Kieltyka

Fleischmann

et al. 2021

Arthritis & Rheumatology

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The discovery of cytokines and their role in immune and inflammatory disease led to the development of a plethora of targeted biologic therapies. Later, efforts to understand mechanisms of cytokine signal transduction led to the discovery of JAKs, which themselves were quickly identified as therapeutic targets. It has been a decade since the first JAK inhibitors (jakinibs) were approved, and there are now 9 jakinibs approved for the treatment of rheumatic, dermatologic, hematologic, and gastrointestinal indications, along with emergency authorization for COVID-19. In this review, we will summarize relevant discoveries that led to first-generation jakinibs and review their efficacy and safety as demonstrated in pivotal clinical studies. We will discuss the next generation of more selective jakinibs, along with agents that target kinase families beyond JAKs. Finally, we will reflect on both the opportunities and challenges ahead as we enter the second decade of the clinical use of jakinibs.

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“…An integrated safety analysis of baricitinib after up to 8.4 years of treatment reported no additional safety concerns 27 . Herpes zoster occurred in approximately 3% of patients, with rates of other adverse events of interest (major adverse cardiovascular events, deep vein thrombosis, gastrointestinal perforation) all reported in less than 1% of patients 27 …”

Section: Infectionsmentioning

confidence: 99%

A comparison of Janus kinase inhibitor safety in rheumatoid arthritis

Nash

Lim²,

Marabani

2021

Int J of Rheum Dis

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The last decade has seen considerable advancement in the treatment options available to patients with rheumatoid arthritis (RA) through the development of oral, small molecules that target and inhibit Janus kinases (JAKi). These drugs have a rapid onset of action, disrupting the Janus kinase/signal transducer and activator of transcription pathway and preventing the production of cytokines involved in inflammatory processes. They have the potential to provide immunomodulatory benefits across a broad range of diseases. This narrative review focuses on the safety profile of tofacitinib, baricitinib, upadacitinib, and filgotinib. Although JAKi have been shown to be effective in the treatment of RA, it is posited that they have different selectivities, which are likely to affect their safety profiles in RA patients. Currently, there are limited long‐term safety data available, with most data coming from randomized controlled trials. However, the data that are available show that upadacitinib and filgotinib may have improved safety profiles. This is particularly true in relation to herpes zoster, venous thromboembolism, and gastrointestinal perforation. Future research is needed to investigate the safety and efficacy of switching between JAKi when a previous JAKi has not been tolerated or has been ineffective.

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Fri0123 safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis Up to 8.4 Years: An Updated Integrated Safety Analysis

Cited by 14 publications

References 0 publications

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

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

A Decade of JAK Inhibitors: What Have We Learned and What May Be the Future?

A comparison of Janus kinase inhibitor safety in rheumatoid arthritis

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