The infection risks of JAK inhibition

Adas, Maryam A; Alveyn, Edward; Cook, Emma; Dey, Mrinalini; Galloway, James; Bechman, Katie

doi:10.1080/1744666x.2022.2014323

Cited by 31 publications

(37 citation statements)

References 77 publications

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“…Patients with RA had a higher risk of serious infection than those with AD or AA during treatment with baricitinib, possibly because 79% and 51% of these former patients were also receiving methotrexate or glucocorticoids, respectively, [ 91 ] and they tended to be, on average, older than patients receiving the drug for dermatological diseases (Table 2 ). Increased vulnerability to serious infection with age is well established [ 118 ] and this was further shown in the baricitinib safety data [ 111 ]. Winthrop et al [ 111 ] also showed that the risk in baricitinib-treated patients was increased in those with abnormal BMI and in those receiving concomitant glucocorticoid therapy.…”

Section: Adverse Events Of Special Interest: Baricitinib Clinical Evi...mentioning

confidence: 92%

Section: Adverse Events Of Special Interest: Baricitinib Clinical Evi...mentioning

confidence: 99%

“…Patients with RA are susceptible to infections (Table 1 ), particularly bacterial infections, most commonly pulmonary, urinary, skin/soft tissue and joint infections, rather than viral or fungal infections [ 45 – 47 , 83 , 84 ]. This increased infectious risk has been attributed to RA itself, comorbid conditions and immunosuppressive therapies used to treat the disease [ 45 , 46 , 83 , 118 , 125 – 128 ]. Indeed, the risk of infection is increased in those with high RA activity, advanced age and male sex, in smokers and with the use of immunosuppressive treatment [ 45 , 118 , 125 – 127 ].…”

Section: Adverse Events Of Special Interest: Baricitinib Clinical Evi...mentioning

confidence: 99%

“…The JAK/STAT pathway is involved in immune regulation, thereby modulating defences against infection [118]. Increased risk of infection versus placebo has been reported with JAKis, with the risk of serious infections being comparable to that of biologics in rheumatologic diseases [118]. In common with all JAKis [119][120][121][122], baricitinib has been associated with upper respiratory tract infections, urinary tract infections, herpes zoster [91], and in patients with AD, herpes simplex [99].…”

Section: Infections and Jak Inhibitionmentioning

confidence: 99%

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A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19

Bieber

Feist²,

Irvine

et al. 2022

Adv Ther

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Baricitinib is an oral, selective inhibitor of Janus kinase (JAK)1/JAK2 that transiently and reversibly inhibits many proinflammatory cytokines. This mechanism is a key mediator in a number of chronic inflammatory diseases; accordingly, baricitinib has been studied and approved for the treatment of several rheumatological and dermatological disorders, as well as COVID-19. This narrative review summarises and discusses the safety profile of baricitinib across these diseases, with special focus on adverse events of special interest (AESI) for JAK inhibitors, using integrated safety data sets of clinical trial data, and puts findings into context with the underlying risk in the respective disease populations, using supporting literature. We show that rates of infection with baricitinib generally reflected the inherent risk of the disease populations being treated, with serious infections and herpes zoster being more frequent in rheumatic diseases than in dermatological disorders, and herpes simplex being reported particularly in atopic dermatitis. Similarly, rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE) and malignancies were generally within or below the ranges reported for the respective disease populations, thereby reflecting the underlying risk; these events were therefore more frequent in patients with rheumatic diseases than in those with dermatological disorders, the latter of whom generally had low absolute risk. AESI were usually more common in patients with risk factors specific for each event. When a population similar to that of ORAL Surveillance was considered, the incidence rate of MACE with baricitinib was numerically lower than that reported with tofacitinib and similar to that of tumour necrosis factor inhibitors. No safety concerns were observed in hospitalised patients with COVID-19 who received baricitinib for up to 14 days. Identifying the patterns and likelihoods of AEs that occur during treatment in large groups of patients with different diseases can help the physician and patient better contextualise the benefit-to-risk ratio for the individual patient.

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Section: Adverse Events Of Special Interest: Baricitinib Clinical Evi...mentioning

confidence: 92%

Section: Adverse Events Of Special Interest: Baricitinib Clinical Evi...mentioning

confidence: 99%

Section: Adverse Events Of Special Interest: Baricitinib Clinical Evi...mentioning

confidence: 99%

Section: Infections and Jak Inhibitionmentioning

confidence: 99%

See 2 more Smart Citations

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19

Bieber

Feist²,

Irvine

et al. 2022

Adv Ther

View full text Add to dashboard Cite

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“…For example, a known class effect for JAKi is an elevated risk of herpes zoster (67)(68)(69)(70). In one recent study, serious infections were more frequent with tofacitinib at a dose of 10 mg twice daily compared to TNF inhibition (71), which contradicts some available evidence pointing to a similar risk of serious infections under JAKi compared to other biological disease-modifying antirheumatic drugs (bDMARDs) (72,73). The risk for opportunistic infections (herpes zoster, tuberculosis) under tofacitinib in this study was higher compared to a TNFinhibitor, and even more so when tofacitinib dose was 10 mg compared to 5 mg.…”

Section: Type I Interferonopathiesmentioning

confidence: 97%

Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review

et al. 2022

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IntroductionAutoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.MethodsA systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.ResultsWe report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).ConclusionThe results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.

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Herpes zoster in patients with inflammatory arthritides or ulcerative colitis treated with tofacitinib, baricitinib or upadacitinib: a systematic review of clinical trials and real-world studies

et al. 2023

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JAK inhibitors (JAKi) are new targeted-synthetic drugs, approved for various immune-mediated inflammatory diseases (IMIDs), including inflammatory arthritides (rheumatoid arthritis—RA, psoriatic arthritis—PsA, ankylosing spondylitis—AS) and ulcerative colitis (UC). JAKi have been associated with increased risk for herpes zoster (HZ), but the relative risk among different JAKi in these IMIDs remains unclear. We aimed to systematically review the incidence of HZ among RA, PsA, AS and UC patients treated with the approved doses of tofacitinib (TOFA), baricitinib (BARI) or upadacitinib (UPA). PubMed, Embase, Scopus, Cochrane and Web-of-Science were searched up to 30 March 2022. Clinical trials and real-world studies (RWS) were included. Outcomes assessed were the incidence rate (/100 patient-years) or/and cumulative incidence of HZ. From 1710 records, 53 clinical trials and 25 RWS were included (RA: 54, PsA: 8, AS: 4, and UC: 12). In clinical trials, the HZ-incidence was higher in TOFA-treated patients with RA (2.2–7.1/100 patient-years) or UC (1.3–7.6/100 patient-years) compared to PsA (1.7/100 patient-years), and with higher doses of TOFA in UC (10 mg/twice daily: 3.2–7.6/100 patient-years vs. 5 mg/twice daily: 1.3–2.3/100 patient-years). Evidence for HZ-risk in JAKi-treated patients with AS and in UPA-treated patients was limited. The HZ-incidence between TOFA and BARI groups in 2 RA RWS did not differ significantly. Concomitant glucocorticoid, but not methotrexate, use in RA increased the HZ-risk. This systematic review showed higher HZ-risk in RA or UC than PsA patients treated with TOFA, in those treated with higher TOFA doses or with concomitant glucocorticoids. Preventive measures and monitoring of JAKi-treated patients with IMIDs are essential in daily practice.

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The infection risks of JAK inhibition

Cited by 31 publications

References 77 publications

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19

Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review

Herpes zoster in patients with inflammatory arthritides or ulcerative colitis treated with tofacitinib, baricitinib or upadacitinib: a systematic review of clinical trials and real-world studies

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