Effectiveness and safety profile of tofacitinib and baricitinib in rheumatoid arthritis patients: results from a 24-month real-life prospective study in Southern-Italy

Tasso, Marco; Bertolini, Nicoletta; Mostacciuolo, Erika; Passavanti, Saverio; Luppino, J. M. E.; Puente, Antonio Del; Peluso, Rosalia; Santelli, Francesco; Scarpa, Raffaele; Costa, Luisa; Caso, Francesco

doi:10.4081/reumatismo.2022.1511

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…Besides all these RCTs, several study groups from different geographic areas have already been published and showing parallel results both each other and RCTs regarding the efficacy of tofacitinib (18)(19)(20)(21)(22)(23). Also, recent data suggest a possible role in tofacitinib in the management of RA-related interstitial lung disease (24,25).…”

Section: Rheumatoid Arthritismentioning

confidence: 81%

Tofacitinib: Current Considerations in the Management of Immune Inflammatory Disorders

Erden¹

2023

qrheumatol

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INVITED REVIEWTofacitinib, the first member of targeted-synthetic disease-modifying antirheumatic drugs, is an oral inhibitor of Janus kinases (JAKs), preferentially JAK-1 and 3. It is an analog of adenosine triphosphate and inhibits several pro-inflammatory cytokines and pathways. Tofacitinib is rapidly absorbed and eliminated mainly via the liver. The efficacy of tofacitinib has been studied extensively in patients with RA patients with different clinical scenarios. Now, tofacitinib is approved in several countries with the indications of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular and systemic juvenile idiopathic arthritis, and ulcerative colitis. Also, studies to assess the efficacy of tofacitinib in patients with several different indications are under consideration. Neutropenia, anemia, elevation of transaminase levels, hyperlipidemia, and increased risk of infections with several causes are well-known side effects. However, recent data from the ORAL Surveillance study shed light on the risk of cardiovascular events and malignancy. In that study, patients with RA over 50 years with at least 1 cardiovascular risk factor were randomized to anti-tumor necrosis factors or tofacitinib; revealing and increased cardiovascular event risk and malignancy (especially lung cancer and lymphoma) in the tofacitinib arm. Although post hoc analysis of the data set suggested a possible link between the history of cardiovascular disease and both cardiovascular and malignancy end-points, FDA, and EMA announced black-box warnings for all JAK inhibitors covering all indications. Obviously, JAK inhibitors, the game changers of the last decade, need further evaluation, especially regarding safety issues.

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Section: Rheumatoid Arthritismentioning

confidence: 81%

Tofacitinib: Current Considerations in the Management of Immune Inflammatory Disorders

Erden¹

2023

qrheumatol

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ToRaRI (Tofacitinib in Rheumatoid Arthritis a Real-Life experience in Italy): Effectiveness, safety profile of tofacitinib and concordance between patient-reported outcomes and physician's global assessment of disease activity in a retrospective study in Central-Italy

D’Alessandro,

Cazzato,

Laurino

et al. 2023

Clin Rheumatol

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Introduction The use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered in daily practice. In consideration of ORAL-Surveillance trial and the new EULAR recommendations, real-world data are needed to assess Jak-Is safety and effectiveness. The multicenter study presented here aimed to evaluate effectiveness and safety of tofacitinib in a real-life cohort. Methods A retrospective analysis was performed from September 2021 to December 2022. Data were collected when tofacitinib was started (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. The primary objective was to analyze the efficacy and safety of tofacitinib. Safety was assessed by recording adverse events (AEs) with and without discontinuation. The secondary objective was to assess the difference between Patient-Reported Outcomes (PROs) and Physician's Global Assessment of disease activity (PhGA). Results 122 patients were included in the study from the following rheumatology Centers: Pisa, Ancona, Florence (two Centers), Siena, and Sardinia. A statistically significant improvement in DAS-28-CRP, CDAI and SDAI score was observed at T3, T6, compared to baseline (p < 0.001). Improvement was confirmed in patients who reach T12. Patients naïve to bDMARDs showed a shorter remission time and higher remission rates. There was also a statistically significant improvement in PROs compared to baseline (p < 0.001). The improvement was rapid and was consistent with PhGA. The 12-month retention rate for tofacitinib was 89.35%. Reasons to stop tofacitinib were: insufficient response (7), gastrointestinal symptoms (2), infection (1), malignancy (1), Zoster (1), pruritus sine materia (1). Conclusions Tofacitinib is safe and effective in our RA cohort. It induces higher remission rates in patients naive to bDMARDs, suggesting that there may be a benefit using it as first-line therapy. Additionally, improvement in PROs was consistent with PhGA scores, demonstrating how tofacitinib affects both the objective and subjective components of disease activity. Key Points1. JAK inhibitors are considered at a similar level as biologic agents in terms of effectiveness.2. After ORAL-Surveillance results, real-world data are needed to assess the benefit/risk profile of Jaki.3. Disagreement between patients and physicians has been previously reported with biologic therapy among patients with rheumatoid arthritis, with patients rating disease activity higher than physicians.4. Jak inhibitors could reduce this discrepancy, due to their mechanism of action.

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Effectiveness and Predictors of Long-Term Treatment Response to Tofacitinib in Rheumatoid Arthritis Cohort: General Analysis and Focus on High-Cardiovascular-Risk Subgroup—A Multicenter Study

Priora,

Becciolini,

Celletti

et al. 2024

Medicina

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Background and Objectives: The treatment landscape for Rheumatoid Arthritis (RA) has evolved significantly with the introduction of Janus kinase inhibitors (JAKi), such as Tofacitinib (TOFA), which offer a new therapeutic option for patients who have failed or are intolerant to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Safety concerns, particularly related to cardiovascular and cancer risks, prompted a need for additional investigation in real-world clinical settings. This study aimed to evaluate the long-term effectiveness and predictors of response to TOFA in two subpopulations of RA patients, categorized by differing cardiovascular risk profiles. Materials and Methods: This was a retrospective, multicenter observational study conducted as part of the BIRRA project, involving 23 Italian rheumatological referral centers. A total of 213 patients diagnosed with RA and treated with TOFA were included, with data collected on baseline demographics, clinical history, disease activity, and comorbidities. Patients were divided into high-risk and low-risk cardiovascular groups based on age (≥65 years) and the presence of at least one cardiovascular risk factor. Disease activity was assessed at baseline, 6 months, and 12 months using DAS28-ESR and DAS28-CRP. Treatment response was evaluated using intention-to-treat (ITT) and per-protocol (PP) approaches. Predictors of low disease activity (LDA) and remission were assessed through logistic regression, and clustering analyses were used to identify subgroups of patients with different therapeutic responses. Results: The study included 213 patients, with 129 classified as high-risk. For the overall cohort, patients achieving LDA and remission at 6 months were 20% and 12%, respectively, for the ITT analysis, and 29% and 14% for the PP analysis. At 12 months, 26% of patients reached LDA, and 17% achieved remission according to ITT, while for the PP analysis, these rates were 30% and 19%, respectively. No significant differences in remission or LDA rates were observed between the high-risk and low-risk groups. In the high-risk subgroup, 17% of patients reached LDA and 9% achieved remission at 6 months (ITT analysis), while these rates increased to 22% and 13%, respectively, in the PP analysis. At 12 months, 22% achieved LDA and 13% achieved remission in the ITT analysis, while 28% and 17% did so in the PP analysis. The reduction in DAS28-ESR and DAS28-CRP scores was significant (p < 0.001) across all time points for both high-risk and low-risk patients. Logistic regression analyses revealed that none of the baseline characteristics—including age, sex, comorbidities, rheumatoid factor, anti-citrullinated protein antibody (ACPA) positivity, initial disease severity, or treatment history—were significant predictors of remission or LDA at 6 or 12 months. The clustering analysis suggested that older patients, particularly those with worse baseline DAS28 scores, tended to show a less favorable response to treatment, potentially indicating impacts of age-related factors such as immunosenescence on therapeutic outcomes. Conclusions: Tofacitinib demonstrated similar effectiveness in both high- and low-risk cardiovascular subgroups of RA patients, with significant reductions in disease activity observed at both 6 and 12 months. Despite safety concerns related to cardiovascular risk, TOFA remained an effective treatment option across patient subgroups, with no significant differences in remission or LDA rates based on cardiovascular risk profiles. Age appeared to negatively impact treatment response, highlighting the role of immunosenescence in RA management. These findings support the use of TOFA as a personalized therapeutic option for RA, emphasizing the need for careful evaluation of cardiovascular and age-related risks in clinical decision-making.

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Effectiveness and safety profile of tofacitinib and baricitinib in rheumatoid arthritis patients: results from a 24-month real-life prospective study in Southern-Italy

Cited by 3 publications

References 18 publications

Tofacitinib: Current Considerations in the Management of Immune Inflammatory Disorders

Tofacitinib: Current Considerations in the Management of Immune Inflammatory Disorders

ToRaRI (Tofacitinib in Rheumatoid Arthritis a Real-Life experience in Italy): Effectiveness, safety profile of tofacitinib and concordance between patient-reported outcomes and physician's global assessment of disease activity in a retrospective study in Central-Italy

Effectiveness and Predictors of Long-Term Treatment Response to Tofacitinib in Rheumatoid Arthritis Cohort: General Analysis and Focus on High-Cardiovascular-Risk Subgroup—A Multicenter Study

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