Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor

Charles‐Schoeman, Christina; Wicker, P.; González-Gay, Miguel Á.; Boy, M.; Zuckerman, Andrea; Soma, Koshika; Geier, Jamie; Kwok, Kenneth; Riese, Richard J.

doi:10.1016/j.semarthrit.2016.05.014

Cited by 124 publications

(82 citation statements)

References 55 publications

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“…47 Similar findings were reported in this analysis of pooled data from phases I-III and LTE studies (data cut-off: 31 March 2015; see online supplementary appendix).…”

Section: Discussionsupporting

confidence: 83%

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

et al. 2017

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ObjectivesTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA.MethodsData were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest.Results6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure.ConclusionThis analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.Trial registration numbers NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT00413699, NCT00661661; Results.

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“…47 Similar findings were reported in this analysis of pooled data from phases I-III and LTE studies (data cut-off: 31 March 2015; see online supplementary appendix).…”

Section: Discussionsupporting

confidence: 83%

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

et al. 2017

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“…Patients treated with JAK inhibitors do not appear to have an increased risk of major adverse cardiac events or stroke 42,45,53,54 .…”

Section: Safety Datamentioning

confidence: 99%

JAK inhibitors in dermatology: The promise of a new drug class

Damsky

King

2017

Journal of the American Academy of Dermatology

380

286

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New molecularly targeted therapeutics are changing dermatologic therapy. JAK-STAT is an intracellular signaling pathway upon which many different pro-inflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors may be a useful therapeutic strategy for these diseases. There is growing evidence that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition may be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

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“…26 In addition, there have been consistent dose-related increases in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) by an average of 10% to 20% which reverses after cessation of therapy. 20,22,26,27 The lipid changes, however, have not translated into a significant increase in cardiovascular events though larger studies are needed to assess the magnitude and significance of any cardiovascular signal. 27 …”

Section: Tofacitinib: a Pan Jak Inhibitormentioning

confidence: 99%

“…20,22,26,27 The lipid changes, however, have not translated into a significant increase in cardiovascular events though larger studies are needed to assess the magnitude and significance of any cardiovascular signal. 27 …”

Section: Tofacitinib: a Pan Jak Inhibitormentioning

confidence: 99%

Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn's Disease

Boland

Vermeire

2017

Gastroenterology Clinics of North America

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Synopsis There is an ongoing unmet need for effective therapies for Crohn’s disease (CD). Treatments for Crohn’s disease continue to evolve from the traditional biologics to novel small molecules with targeted mechanisms directed towards pathways that are dysregulated in Crohn’s disease. There are multiple emerging mechanisms of action including JAK inhibition, Smad7 inhibition, and Sphingosine-1-phosphate (S1P) receptor modulators that are administered as oral medications, and small molecules represent the next generation of therapies for Crohn’s disease.

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Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor

Abstract: Tofacitinib was associated with a low incidence of CV events in a large Phase 3 program, including LTE studies. Further long-term studies are underway.

Cited by 124 publications

References 55 publications

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

JAK inhibitors in dermatology: The promise of a new drug class

Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn's Disease

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