Abstract:Tofacitinib is an oral Janus kinase (JAK) inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety/tolerability of tofacitinib have been extensively evaluated as monotherapy and combination therapy in multiple, randomised, multicentre studies in patients with RA. Tofacitinib as monotherapy (as first-and second-line treatment) or as combination with methotrexate (MTX) or other csDMARDs as second-and third-line treatment is effective and generally well tolerated in patients wit… Show more
“…Tofacitinib significantly reduced disease activity, with 82% achieving the treatment target at follow-up. In the clinical trials, the treatment target was achieved according to DAS28-ESR in up to 47.5% [13][14][15] while in real-world studies, it is up to 58% [16][17].…”
Background: Tofacitinib is the first Janus kinase (JAK) inhibitor approved for treating rheumatoid arthritis (RA). Several clinical trials have evaluated the safety and effectiveness of tofacitinib in adult patients with moderately to severely active RA. Real-world studies provide invaluable insights into routine clinical practice. We aim to assess the clinical efficacy and safety of RA patients.Methods: Over a period of two years, we included 50 consecutive RA patients who were treated with tofacitinib. Clinical disease activity, assessed by disease activity score (DAS) 28 -erythrocyte sedimentation rate (ESR), as well as adverse events (AEs) were evaluated.Results: A total of 50 patients (84% female) were enrolled in the study. The mean age at initiation of tofacitinib was 48.54 ± 15.97 years. The mean time of treatment with tofacitinib was 18.06 ± 2.04 months. Patients were treated with tofacitinib 5 mg BID with 32% receiving tofacitinib as monotherapy. A total of 74% of the patients had been prescribed at least one biological treatment. The treatment target was achieved in 42 patients (82%). Baseline characteristics and previous treatment regimens did not predict clinical response to tofacitinib. Fifteen patients discontinued the treatment: seven due to ineffectiveness, four due to pregnancy, and five due to adverse events. The most common infectious adverse event was herpes zoster (4%) while the most common observed laboratory abnormalities were elevation in low density lipoprotein (LDL) and high density lipoprotein (HDL) in 6% and 8% of the patients, respectively. Conclusion: Our results indicate that tofacitinib is effective in real-world settings even as monotherapy. The treatment target was attained by 82% of the patients on tofacitinib. The safety profile of tofacitinib was generally consistent with previous studies.
“…Tofacitinib significantly reduced disease activity, with 82% achieving the treatment target at follow-up. In the clinical trials, the treatment target was achieved according to DAS28-ESR in up to 47.5% [13][14][15] while in real-world studies, it is up to 58% [16][17].…”
Background: Tofacitinib is the first Janus kinase (JAK) inhibitor approved for treating rheumatoid arthritis (RA). Several clinical trials have evaluated the safety and effectiveness of tofacitinib in adult patients with moderately to severely active RA. Real-world studies provide invaluable insights into routine clinical practice. We aim to assess the clinical efficacy and safety of RA patients.Methods: Over a period of two years, we included 50 consecutive RA patients who were treated with tofacitinib. Clinical disease activity, assessed by disease activity score (DAS) 28 -erythrocyte sedimentation rate (ESR), as well as adverse events (AEs) were evaluated.Results: A total of 50 patients (84% female) were enrolled in the study. The mean age at initiation of tofacitinib was 48.54 ± 15.97 years. The mean time of treatment with tofacitinib was 18.06 ± 2.04 months. Patients were treated with tofacitinib 5 mg BID with 32% receiving tofacitinib as monotherapy. A total of 74% of the patients had been prescribed at least one biological treatment. The treatment target was achieved in 42 patients (82%). Baseline characteristics and previous treatment regimens did not predict clinical response to tofacitinib. Fifteen patients discontinued the treatment: seven due to ineffectiveness, four due to pregnancy, and five due to adverse events. The most common infectious adverse event was herpes zoster (4%) while the most common observed laboratory abnormalities were elevation in low density lipoprotein (LDL) and high density lipoprotein (HDL) in 6% and 8% of the patients, respectively. Conclusion: Our results indicate that tofacitinib is effective in real-world settings even as monotherapy. The treatment target was attained by 82% of the patients on tofacitinib. The safety profile of tofacitinib was generally consistent with previous studies.
“…However, the individual trials were not powered to examine rare outcomes such as infections. Long-term extension studies (LTE) and registry data are needed to further understand the risks of rarer outcomes [ 19 ]. Figure 2.…”
Introduction
Janus Kinase inhibitors (JAKi) have shown to be highly effective in the treatment of immune-mediated inflammatory diseases. As with all immunomodulatory therapies, careful assessment of any treatment-associated infection risk is essential to inform clinical decision-making.
Areas covered
We summarize current literature on infection rates among the licensed JAKi using published phase II/III trial results, post-licensing and registry data.
Expert opinion
licensed JAKi show increased risk of infection across the class compared to placebo, most commonly affecting respiratory and urinary tracts, nasopharynx and skin. This risk is dose-dependent. Risks are similar at licensed JAKi doses to that seen with biologic therapies. The risk is compounded by other risk factors for infection, such as age and steroid co-prescription. Herpes zoster reactivation is more common with JAKi compared to other targeted immune modulation, making screening for varicella exposure and vaccination in appropriate cohorts an advisable strategy. Crucially, these small risk increases must be balanced against the known harms (including infection) of uncontrolled autoimmune disease. JAKi are a safe and potentially transformative treatment when used for appropriately selected patients.
“…Tofacitinib is a potent pan-JAK antagonist that is notably more selective against JAK1 and JAK3, which are critical in Th2 signaling, than against JAK2 and TYK2 [96]. Experimental data obtained in mouse model of pulmonary eosinophilia, show that systemic administration of the JAK3 inhibitor tofacitinib (CP-690550), approved for the treatment of rheumatoid arthritis, ulcerative colitis and moderate-to-severe chronic plaque psoriasis [97][98][99][100][101][102][103], effectively inhibited antigen-induced pulmonary eosinophil influx, IL-13 and eotaxin expression [99]. These data are consistent with the previous demonstration that JAK3 −/− mouse models failed to exhibit efficient recruitment of Th2 cells to the lungs following antigen challenge [104].…”
Section: Jak-inhibitors Targeting Type 2 Cytokine Pathwaysmentioning
Bronchial asthma and its frequent comorbidity chronic rhinosinusitis (CRS), are characterized by an inflammatory process at lower and upper respiratory tract, with a variability in terms of clinical presentations (phenotypes) and distinct underpin pathophysiological mechanisms (endotypes). Based on the characteristics of inflammation, bronchial asthma can be distinguished into type 2 (eosinophilic) or nontype 2 (noneosinophilic) endotypes. In type 2 asthma endotype, the pathogenic mechanism is sustained by an inflammatory process driven by Th2 cells, type 2 innate lymphoid cells (ILC2) and type 2 cytokines, which include interleukin (IL)-4, IL-5, IL-9 and IL-13. The definition of asthma and chronic rhinusinusitis phenotype/endotype is crucial, taking into account the availability of novel biologic agents, such as monoclonal antibodies targeting the classical type 2 cytokines. Recently, new therapeutic strategies have been proposed and analyzed in preliminary clinical trials. Among them Janus kinase (JAK) inhibitors, now largely used for the treatment of other chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases, is receiving great relevance. The rationale of this strategy derives from the data that JAK is a tyrosine kinase involved in the signaling of T cell receptor and of several cytokines that play a role in allergic respiratory disease, such as IL-2, IL-4 and IL-9. In this review, we discuss whether treatment with biological agents and JAK inhibitors may be equally effective in controlling type 2 inflammatory process in both asthma and CRS.
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