Effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor level and morning stiffness time in patients with refractory rheumatoid arthritis / 中国医师杂志

Objective:To investigate the effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor (RF) level and morning stiffness time in patients with refractory rheumatoid arthritis (RA).Methods:A total of 120 patients with refractory RA diagnosed and treated in the First Affiliated Hospital of Hebei North University from June 2019 to June 2020 were selected as the study subjects, and they were randomly divided into three groups by random number table method: etanercept group, etanercept+ methotrexate group, and tofacitinib+ methotrexate group, with 40 patients in each group. The etanercept group was given etanercept treatment, the etanercept+ methotrexate group was given etanercept combined with methotrexate treatment, and the tofacitinib+ methotrexate group was given tofacitinib combined with methotrexate treatment. The clinical efficacy (12 W, 24 W and 48 W of treatment), disease activity, RF level, morning stiffness time and incidence of adverse reactions were compared among the three groups.Results:Comparison of the total clinical effective rate of the three groups: the total clinical effective rate of the etanercept+ methotrexate group and the tofacitinib+ methotrexate group was higher than that of the etanercept group (both P<0.05), and the tofacitinib+ methotrexate group was higher than that of the etanercept+ methotrexate group ( P<0.05). After treatment, the clinical symptoms and disease activity scores (DAS28) in the etanercept+ methotrexate and tofacitinib+ methotrexate groups were significantly improved compared with the etanercept group (all P<0.05), and the improvements in the tofacitinib+ methotrexate group were more significant than those in the etanercept+ methotrexate group ( P<0.05). After treatment, the erythrocyte sedimentation rate (ESR), RF and C-reactive protein (CRP) levels were lower in the etanercept+ methotrexate and tofacitinib+ methotrexate groups than those in the etanercept groups (all P<0.05), and the ESR, RF and CRP levels in the tofacitinib+ methotrexate groups were lower than those in the etanercept+ methotrexate group (all P<0.05). There was no significant difference in the incidence of total adverse reactions among 3 groups (7.50% vs 12.50% vs 12.50%) ( P>0.05). Conclusions:Tofacitinib combined with methotrexate can effectively improve the disease activity, RF level and morning stiffness time in patients with refractory RA, with high safety, which is worthy of clinical application and promotion.

Efficacy and safety of different Janus kinase inhibitors combined with methotrexate for the treatment of rheumatoid arthritis: a single-center randomized trial

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

Efficacy and safety of Tofacitinib in treating the elderly rheumatoid arthritis / 中华老年医学杂志

Objective:To observe the efficacy and safety of Tofacitinib in treating elderly rheumatoid arthritis(RA), in order to provide clinical evidence.Methods:In the randomized control trial, a total of 90 elderly RA patients admitted to the Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2019 to January 2021 were selected and divided into Methotrexate group(MTX group, MTX 10mg, qw, n=45)and Tofacitinib group(TOF group, oral 5mg, bid, n=45). The efficacy and safety of the two groups were evaluated at week 12.The primary endpoint was the proportion of patients meeting the American College of Rheumatology 50%(ACR50)improvement response criteria at week 12.Secondary endpoints included ACR20/70 improvement response, proportion of patients who met treat-to-target(T2T)criteria, including Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28-ESR), Disease Activity Score in 28 joints using C-reactive protein level(DAS28-CRP), clinical disease activity index(CDAI), and simplified disease activity index(SDAI), and patient-reported outcomes(PROs)which included changes compared to baseline in pain visual analog scale(VAS)and Health Assessment Questionnaire Disability Index(HAQ-DI)score, at week 12.Safety outcomes including drug-related adverse events, serious adverse events, dropping out due to adverse events, and deaths were assessed throughout.Results:Five patients in each group withdrew from the trial due to adverse events, and the number of patients who finally completed the observation was 40 in each group.At week 12, the ACR50 response rate was higher in TOF group than in MTX group[35%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018)], achieving the primary endpoint.When comparing TOF vs.MTX group, the ACR20 response rate[55%(22/40) vs.25%(10/40), χ2=7.500, P=0.006]and ACR70 response rate[25%(10/40) vs.7.5%(3/40), χ2=4.501, P=0.034], and proportions of indexes of disease remission including DAS28-ESR<2.6[25%(11/40) vs.7.5%(3/40), χ2=4.501, P=0.034], or DAS28-CRP<2.6[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], or CDAI≤2.8[30%(12/40) vs.10%(4/40), χ2=5.000, P=0.025], or SDAI≤3.3[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], and the proportions of patients with low disease activity including DAS28-ESR≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or DAS28-CRP≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or CDAI≤10[37.5%(15/40) vs.17.5%(7/40), χ2=4.013, P=0.045], or SDAI≤11[37.5%(15/40) vs.15%(6/40), χ2=5.230, P=0.022], as well as changes compared to baseline data in pain VAS[(26.51±8.32)scores vs.(14.16±4.39)scores, t=8.371, P<0.001]and in HAQ-DI score(0.65±0.24 vs.0.32±0.06, t=9.387, P<0.001)were all better in the TOF group than in the MTX group at week 12.During the 12-week observation period, the number of patients with infection and hyperlipidemia was higher in TOF group than in MTX group, while the number of patients with abnormal blood cell count and liver function was lower than that in MTX group, but the differences were not statistically significant(all P<0.05). Conclusions:Tofacitinib has good efficacy and safety in the elderly RA.In patients over 70 years of age who are at high risk of infection, tofacitinib should be used with caution.

Caracterización del uso de tofacitinib como tratamiento para COVID-19 / si

Objetivo: El propósito principal de este estudio es caracterizar y comparar la población que recibió tofacitinib con aquella que no fue tratada con este fármaco para la COVID-19 en la Clínica Unión Médica del Norte, durante el año 2020. Métodos: Se realizó un estudio de tipo observacional, retrospectivo transversal de tipo exploratorio y de fuente secundaria. Se analizaron las características de los participantes y su tratamiento en relación con los parámetros de laboratorio y las características clínicas. Resultados: Se incluyeron 507 pacientes ingresados en la unidad de COVID-19 de la Clínica Unión Médica del Norte. Se determinó que las defunciones fueron menores en el grupo que se medicó con tofacitinib (6,45%) en comparación con el grupo que no utilizó dicho fármaco. Asimismo, los medicados con esta terapia ameritaron en menos proporción soporte ventilatorio, sin embargo, hubo más proporción de ingresos a la Unidad de Cuidados Intensivos. Además, se identificó una reducción mayor en la glucemia en aquellos pacientes medicados con tofacitinib, aunque mayores niveles de ferritina y dímero D. Conclusiones: El fármaco tofacitinib puede actuar de manera beneficiosa en relación con la mortalidad y la reducción del uso de ventilación mecánica. En adición, podría colaborar con la evolución de los pacientes. No obstante, nuestra investigación no es concluyente. Es necesario realizar futuras investigaciones confirmatorias de la eficacia de la terapia con tofacitinib para los pacientes con COVID-19.

Objective: The main purpose of this study is to characterize and compare the population that received tofacitinib with those that were not treated with the drug for COVID-19 at the Clínica Unión Médica del Norte, in 2020. Methods: An observational, retrospective, cross-sectional, exploratory, and secondary source study was conducted. A comparison was made between clinical and sociodemographic characteristics, laboratory results and their treatment option. Results: Five hundred and seven patients admitted to the COVID-19 unit of the Clínica Unión Médica del Norte were included. It was determined that lower death rates were registered in the group that received tofacitinib (6.45%) compared to the group that did not use the drug. Likewise, those receiving this therapy required less mechanical ventilation, however, a higher proportion of these patients were admitted to the Intensive Care Unit. In addition, a greater reduction in glycaemia was identified in the patients receiving tofacitinib, but they had higher levels of ferritin and D-dimer. Conclusions: Tofacitinib may be beneficial in terms of mortality rates and reduction in the use of mechanical ventilation. Furthermore, it is promising with respect to positive patient progression. However, our research is not conclusive. Future confirmatory research is needed on the efficacy of tofacitinib therapy for COVID-19 patients.

D-Dimer trend in a long-term rheumatoid arthritis patient with tofacitinib treatment and recent COVID-19 infection

The SARS-CoV-2 virus was first identified in December 2019, the infection was named COVID-19. The initial symptoms and evolution of the disease have been described over the past year. The virus has been shown to increase the risk of thromboembolic events due to the hypercoagulable state triggered by systemic endothelial inflammation. We present the case of a patient with a history of rheumatoid arthritis under prolonged treatment with tofacitinib, who presented COVID-19 and subsequently developed a hypercoagulable state of approximately 6 months' duration. The possible association between viral infection and the use of tofacitinib is debated.

El virus SARS-CoV-2 se identificó por primera vez en diciembre de 2019; la infección se denominó COVID-19. Los síntomas iniciales y la evolución de la enfermedad se han descrito durante el último anno. Se ha demostrado que el virus aumenta el riesgo de eventos trom-boembólicos debido al estado de hipercoagulabilidad desencadenado por la inflamación endotelial sistêmica. Se presenta el caso de un paciente con antecedente de artritis reuma-toide en tratamiento prolongado con tofacitinib, que presentó COVID-19 y posteriormente desarrolló un estado de hipercoagulabilidad de aproximadamente seis meses de duración. Se debate la posible asociación entre la infección viral y el uso de tofacitinib.

The efficacy of tofacitinib combined with leflunomide in the treatment of rheumatoid arthritis and its effect on serum janus kinase/signal transduction and activator of transcription signaling pathway-related proteins and matrix metalloproteinases levels / 中华风湿病学杂志

Objective:To investigate the clinical efficacy of Tofacitinib combined with leflunomide in the treatment of rheumatoid arthritis (RA) and its effects on Janus Kinase (JAK)/signal transduction and activator of transcription (STAT) signaling pathway-related proteins and Matrix metalloproteinase levels in serum of patients with RA.Methods:This was a prospective case-control study. A total of 80 patients with RA in our hospital from March 2020 to September 2021 were included into the study. They were divided into observation group and control group by random number table method, with 40 cases in each group. The patients in observation group were treated with Tofacitinib combined with leflunomide, while the patients in control group were treated with leflunomide alone. After 12 weeks of continuous treatment, the curative effect of the two groups was observed. Typical clinical manifestation [including Visual analogue scale (VAS) score of joint pain, number of tenderness joints, number of swollen joints, time of morning stiffness], disease activity score uses 28 joint counts (DAS28) scores, the MOS item short from health survey (SF-36) total scores and serum JAK3, STAT3, interleukin (IL)-6, IL-17 and matrix metalloproteinase (MMPs) levels were compared between the two groups before and after treatment. The adverse effects of the two groups were also analyzed. Chi-square test, paired sample t test, independent sample t test and Fisher exact probability method were used for statistical analysis. Results:After 4, 8 and 12 weeks of treatment, the american college of rheumatology (ACR)20 compliance rates in the observation group were 37.5%(15/40), 62.5%(25/40) and 80.0%(32/40), respectively, which were significantly higher than those in the control group at the same period [17.5%(7/40), 37.5%(15/40), 57.5%(23/40); χ2=4.01, P=0.045; χ2=5.00, P=0.025; χ2=4.71, P=0.030]. After 8 and 12 weeks of treatment, the ACR50 compliance rates in the observation group were [35.0%(14/40) and 47.5%(19/40), respectively, which were significantly higher than those in the control group at the same period 15.0%(6/40) and 20.0%(8/40), χ2=4.27, P=0.039; χ2=6.76, P=0.009]. After treatment, the joint pain VAS score, number of tenderness joints, number of swollen joints, DAS28 scores and SF-36 total scores in the observation group were lower than those in the control group( t=5.55, P<0.001; t=9.98, P<0.001; t=11.77, P<0.001; t=4.50, P<0.001; t=5.28, P<0.001), and time of morning stiffness was shorter than that in the control group ( t=4.76, P<0.001). After treatment, The serum levels of JAK3, STAT3, IL-6, IL-17, MMP-3, MMP-9 and MMP-13 in the obser vation group were (2 354±476) pg/ml, (1.04±0.17) ng/ml, (12.4±2.8) pg/ml, (30±5) pg/mL, (65±14) μg/L, (76±12) μg/L, (11.5±1.8) μg/L, which were lower than those in control group [(2 715±584) pg/ml (1.22±0.29) ng/mL, (16.8±3.6) pg/ml, (40±7) pg/ml, (98±15) μg/L, (123±20) μg/L, (14.9±2.8) μg/L, t=3.03, P<0.05; t=3.39, P<0.05; t=6.10, P<0.05; t=7.35, P<0.05; t=10.17, P<0.05; t=12.74, P<0.05; t=6.46, P<0.05]. The adverse reaction rate of the observation group [35.0%(14/40)] had no statistically significant difference compared with that in the control group [27.5%(11/40)]( χ2=0.52, P=0.469). Conclusion:The overall effect of Tofacitinib com bined with leflunomide in the treatment of RA is satisfactory and it is a safe and effective way to improve the clinical manifestation, disease activity and quality of life of patients with RA. The effect may be related to the significant down-regulation of the expression levels of Serum JAK/STAT signaling pathway-related Proteins and MMPs.

The mechanism, efficacy and safety of Tofacitinib on the treatment of juvenile idiopathic arthritis / 中华实用儿科临床杂志

Juvenile idiopathic arthritis(JIA) is one of the most common chronic connective tissue diseases characterized by unknown etiologic arthritis with the onset before the age of 16 years and disease course for more than 6 weeks.JIA may be accompanied by impairment of multiple organ function.Recent studies have shown the important role of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in the pathogenesis of JIA.Tofacitinib is an oral Janus kinase(JAK) inhibitor approved by Food and Drug Administration (FDA) in 2012 for the effective treatment of rheumatoid arthritis.However, there is little clinical evidence for the use of Tofacitinib in pediatrics.This review aims to clarify the mechanisms, efficacy and safety of Tofacitinib on the treatment of JIA.

Recent research on tofacitinib in the treatment of pediatric rheumatic diseases / 中国当代儿科杂志

Tofacitinib is a Janus kinase inhibitor and can block the Janus kinase-signal transducer and activator of transcription signal transduction pathway and reduce the production and release of a variety of cytokines. It has great potential in the treatment of various rheumatic diseases with a rapid onset of action and can reduce corticosteroid dependence and related adverse events. The therapeutic effect of tofacitinib in adult patients has been confirmed, and it has been increasingly used in pediatric patients in recent years. This article reviews the clinical application of tofacitinib in the treatment of pediatric autoimmune diseases.

Optimized synthesis process of tofacitinib citrate / 中国药科大学学报

@#In order to improve the yield and simplify the operation, the synthesizing process of JAK3 inhibitor tofacitinib citrate was improved based on the analysis of the methods previously published.Using 2, 4-dichloro-7H-pyrrolo [2, 3-d] pyrimidine and (3R, 4R)-1-benzyl-N, 4-dimethylpiperidin-3-amine dihydrochloride as starting materials, tofacitinib citrate was obtained through four steps of nucleophilic substitution, catalytic transfer hydrogenation, cyanide acetylation and citrate salt, and its crystal form was consistent with the original research.After optimization, the yield was better than those reported in literature, and the mild reaction conditions were suitable for industrial production.

Clinical application progress of tofacitinib in rheumatoid arthritis / 中国基层医药

Tofacitinib is a novel targeted drug for the treatment of rheumatoid arthritis. With the entry into the medical insurance catalogue, the drug will usher in a new era. This paper reviews the effectiveness and safety of tofacitinib in the treatment of rheumatoid arthritis. Generally speaking, tofacitinib has definite efficacy, few adverse reactions, and controllable safety. Tofacitinib has an advantage over biological agents, that is, tofacitinib can be orally administered. Therefore, tofacitinib is especially developed for patients who have a poor response to or who are intolerant to disease-modifying antirheumatic drugs and biological agents. However, the effectiveness and safety of tofacitinib in a Chinese population need to be confirmed by more studies.

Research advances of tofacitinib in the treatment of ulcerative colitis / 中国药房

Ulcerative colitis （UC）is a chronic inflammatory bowel disease caused by multiple factors ，and its etiology and pathogenesis remain unclear . Tofacitinib，a small molecule rapidly absorbed by oral administration ，treats UC primarily by inhibiting Janus kinase （JAK）. Tofacitinib has been approved by the FDA and the European Medicines Agency for the treatment of moderate to severe UC . Many clinical studies on tofacitinib in the treatment of UC have been carried out abroad ，but there is no relevant report on its use in UC in China . This paper summarizes the relevant research advances of tofacitinib in the treatment of UC from its mechanism ，clinical application and safety . The results show that tefatinib mainly treats UC by inhibiting the expression of JAK and proinflammatory factors , regulating the overexpressed signaling transducers and activators of transcription , and repairing the intestinal mucosal barrier . Tofacitinib has good clinical efficacy ，but safety studies have shown that the risks of herpes zoster and thrombosis should not be ignored ，and the drug should be used with caution in pregnant ，children，adolescents， and elderly patients . The efficacy and safety of tofacitinib in Chinese population should be further studied in the future ，since it has not been used in UC patients in China .

Treatment of psoriatic arthritis with tofacitinib: 5 cases and literature review / 中华风湿病学杂志

Objective:To investigate the efficacy and safety of tofacitinib (TOF) in the treatment of psoriatic arthritis (PsA).Methods:The clinical data of 5 patients with PsA from September 2018 to December 2020 in People's Hospital of Xinjiang Uygur Autonomous Region were collected. Five patients were treated with a variety of disease-modifying anti-rheumatic drugs (DMARDs), two of them had ever been treated with biologic disease-modifying antirheumatic drugs (bDMARDs) [recombinant human tumor necrosis factor-alphareceptor Ⅱ: IgG Fc (rhTNFR: Fc, Adalimumab], but failed to show efficacy or relapse after drug withdrawal. Multiple joints were involved in 2 patients. These five patients were treated with tofacitinib. Their data were collected and analyzed 3-month and 6-month after treatment respectively, including the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), severity of pain measured by visual analogue scale (VAS), joint pain count (TCJ), joint swelling count (SCJ), health assessment questionnaire (HAQ), 28 joint disease activity score (DAS28 CRP), psoriasis area and severity index (PASI), and PsA disease activity index (DAPSA). Adverse reactions were observed and analyzed.Results:These 5 cases were treated with TOF 5 mg twice daily. Three months after treatment, swelling joints count and psoriatic rash were significantly improved, and pain was significantly relieved in 4 cases. Six months after treatment, the ESR, CRP, VAS, TCJ, SCJ, HAQ, DAS28 CRP, PASI, and DAPSA decreased further. According to DSA28-CRP score, peri-pheral joints involvement of 3 cases were improved, and 2 cases reached low disease activity state. The overall effective of PASI were observed in 4 cases. According to the DAPSA score, 1 case reached the PsA disease remission state and 4 cases reached the PsA low disease activity state. No remarkable adverse reactions occurred.Conclusion:With good therapeutic effect and less adverse reactions, TOF is a potential treatment option for PsA.

Tratamiento con tofacitinib en adolescentes con alopecia areata / Tofacitinib as a treatment of alopecia areata in adolescents

Resumen Introducción: Actualmente no existe un tratamiento estandarizado para la alopecia areata (AA) grave. Se han reportado numerosos casos exitosos del uso de tofacitinib; sin embargo, no existen publicaciones en México. En este trabajo se reportan cuatro casos de pacientes mexicanos con AA grave tratados con tofacitinib oral. Métodos: Serie de casos de adolescentes con alopecia grave tratados con tofacitinib oral. Para determinar la respuesta al tratamiento se utilizó la Escala de gravedad de alopecia (Severity of alopecia tool). Resultados: Se incluyeron cuatro pacientes de entre 13 y 19 años con AA. En todos los casos se observó crecimiento de cabello y disminución de la gravedad de la alopecia después del tratamiento con tofacitinib. En dos pacientes se observó una respuesta intermedia (del 51 al 90%), y en los otros, moderada (del 6 al 50%), sin efectos adversos serios. Las limitaciones del estudio fueron el tamaño reducido de la muestra y la naturaleza retrospectiva de la recolección de los datos. Conclusiones: El tofacitinib demostró ser una buena alternativa de tratamiento para la AA, total y universal, refractarias a otras terapias.

Abstract Background: Currently, no standardized treatment for severe alopecia areata (AA) exists. Numerous successful cases of the use of tofacitinib have been reported in the world literature, but not in Mexico. Four Mexican adolescents with severe AA treated with oral tofacitinib are reported in the present work. Methods: Series of cases of adolescents with severe AA treated with oral tofacitinib. The severity of alopecia tool was used to determine the response to treatment. Results: Four patients from 13 to 19 years old, were included. In all cases, hair growth was observed, and the alopecia severity decreased after the treatment with tofacitinib. In two patients, an intermediate response (from 51 to 90%) was observed; in the other, a moderate response (from 6 to 50%) was observed, without serious adverse effects. The limitations of the study were the small sample size and the retrospective nature of data collection. Conclusions: Tofacitinib showed to be a good treatment alternative for AA, total and universal, refractory to other therapies.

Efficacy of Oral Tofacitinib in Patients with Alopecia Areata: Tofacitinib Was Ineffective for Recalcitrant Alopecia Totalis of a Long Duration / 대한피부과학회지

No abstract available.

The Effect and Safety of Tofacitinib for Patients with Moderate to Severe Psoriasis: A Meta-Analysis of Randomized Controlled Trials / 中国药学杂志

OBJECTIVE: To review systematically the effect and safety of tofacitinib for patients with moderate to severe psoriasis. METHODS: Relevant studies were published until May 16, 2018 were identified through The Cochrane Library, PubMed, Embase, Clinical Trials.gov, CNKI, Wanfang, CBM and other web knowledge databases. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then we performed statistical analyses using the Review Manager 5.2 and Stata 12.0 software. RESULTS: Eight randomized controlled trials that compared tofacitinib vs placebo were included in the study. The final Meta-analysis included a total of 3 308 patients with psoriasis. Tofacitinib was associated with reductions in psoriasis area and severity index 75% (RR 3.27, 95%CI1.79-5.98, P=0.000 1), psoriasis area and severity index 90% (RR 12.61, 95%CI7.66-20.76, P<0.000 01), physician′s global assessment (RR 4.38, 95%CI3.51-5.47, P<0.000 01). A safety analysis showed that tofacitinib increased the risk of hypercholesterolemia (RR 2.57, 95%CI1.22-5.38, P=0.01) and tended to associate with increasing the risk of herpes zoster (RR 3.20, 95%CI0.86-11.91, P=0.08). CONCLUSION: Tofacitinib is effective and relatively safe for patients with psoriasis. Therefore, tofacitinib may be a promising treatment option for patients with moderate to severe psoriasis who had previously an inadequate response to the conventional synthetic treatment.

Tofacitinib, an oral Janus kinase inhibitor, in patients from Colombia with rheumatoid arthritis: Pooled efficacy and safety analyses of data from phase III studies / Tofacitinib, un inhibidor oral de la janus kinasa, en pacientes colombianos con artritis reumatoide: análisis de eficacia y seguridad de los estudios de fase III

ABSTRACT Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objective: To conduct a post hoc analysis of tofacitinib efficacy and safety in Colombian patients enrolled in global phase III studies. Methods: Data were pooled from Colombian patients with RA across four phase III tofacitinib studies: ORAL Sync, ORAL Scan, ORAL Solo, and ORAL Start. Patients received tofacitinib 5 or 10 mg twice daily, methotrexate (ORAL Start only), or placebo as single therapy (ORAL Start and ORAL Solo), or in combination with csDMARDs (ORAL Sync and ORAL Scan). Data were pooled from three studies with similar patient populations (Sync, Scan, Solo) for efficacy analyses, and from all studies for safety analyses, up to Month 24. The efficacy analysis excluded ORAL Start due to the methotrexate-naive patient population, and placebo and methotrexate groups, due to low patient numbers. Results: Data pooled included 77 patients for efficacy, and 125 for safety analyses. Tofacitinib-treated patients showed improved American College of Rheumatology 20/50/70 response rates, a mean Disease Activity Score 28-4 (erythrocyte sedimentation rate), and a mean change from baseline in Health Assessment Questionnaire-Disability Index. Improvements were sustained in Months 12-24, although patient numbers were low post-Month 12. The most frequently reported adverse events were anemia, headache, influenza, and increased blood creatine phosphokinase. No tuberculosis cases, serious adverse events, or deaths were reported, and few cases of herpes zoster or malignancies occurred. Conclusions: Tofacitinib reduced RA signs and symptoms, and improved physical function. The efficacy and safety of tofacitinib in this Colombian sub-population were consistent with data from global phase III studies.

RESUMEN Introducción: Tofacitinib es un inhibidor oral de la janus kinasa para el tratamiento de la artritis reumatoide (AR). Objetivo: Análisis post hoc para evaluar la eficacia y seguridad de tofacitinib en los pacientes colombianos que participaron en los estudios globales de fase III. Métodos: La información se obtuvo de los pacientes colombianos con AR que participaron en 4 de los estudios de tofacitinib de fase III: ORAL Sync, ORAL Scan, ORAL Solo y ORAL Start. Los pacientes recibieron tofacitinib 5 o 10 mg 2 veces al día, ya sea en monoterapia (ORAL Start y ORAL Solo) o en combinación con csDMARDs (ORAL Scan y ORAL Sync), metotrexate (ORAL Start) o placebo. Para el análisis de eficacia se utilizaron 3 estudios que incluyeron poblaciones similares (Sync, Scan y Solo) y para el análisis de seguridad se utilizaron todos los estudios, hasta el mes 24. El análisis de eficacia excluyó tanto el estudio ORAL Start debido a población metotrexate naive como a los grupos placebo o metotrexate debido al bajo número de pacientes. Resultados: Se incluyeron 77 pacientes para el análisis de eficacia y 125 para seguridad. Los pacientes tratados con tofacitinib mostraron mejorías en las tasas de respuestas del American College of Rheumatology (ACR) 20/50/70, en el promedio del Disease Activity Score (DAS) 28-4 (velocidad de sedimentación globular) y en el cambio promedio desde la basal en el Health Assessment Questionnaire-Disability Index (HAQ-DI). Las mejorías fueron sostenidas desde el mes 12 al mes 24, aunque el número de pacientes luego del mes 12 fue bajo. Los eventos adversos más frecuentemente reportados fueron anemia, cefalea, influenza e incremento de la creatin-fosfoquinasa sérica. No se reportaron casos de tuberculosis, eventos adversos serios o muertes. Ocurrieron casos poco frecuentes de herpes zoster y malignidades. Conclusiones: Tofacitinib redujo los signos y síntomas de la AR y mejoró la función física. La eficacia y seguridad en esta subpoblación colombiana fue consistente con los resultados de los pacientes que participaron en los estudios globales de fase III.

Emerging Therapies: What Are Promising in the Near Future? / 대한소화기학회지

The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective. Additionally, vedolizumab can be used in patients already failed an anti-TNF therapy. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23. Ustekinumab will be a clinically effective agent to use in medically-refractory Crohn's disease especially as a second line drug. Tofacitinib is an oral, small molecule that inhibits JAK1, JAK3 and in a lesser extent, JAK2. Perhaps the most attractive things of these JAK inhibitors is that they are given orally instead of parenterally. Early results showed that patients with moderately to severely active ulcerative colitis receiving tofacitinib were more likely to achieve remission at 8 weeks than those receiving placebo. However, these results have not been as robust in Crohn's disease. Much of the positioning will depend on the safety profile such as opportunistic infection and atherogenic risk. The challenges for the future are to determine the therapeutic drug monitoring-guided dose optimization, optimal timing and drug combinations to produce the most effective, and safest outcomes for IBD patients.

Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis / 中华医学杂志(英文版)

Background@#Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.@*Methods@#ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout.@*Results@#ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population.@*Conclusions@#Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population.@*Clinical Trial Identifier@#NCT00856544 and NCT00413699.

Treatment interruption of biological drugs and tofacitinib in rheumatoid arthritis: A systematic review of case reports

The aim of this study was to evaluate interruption of treatment with biological drugs and tofacitinib due to adverse events in patients with rheumatoid arthritis. A systematic review was performed in the electronic databases MEDLINE, Cochrane, Scopus, CRD, IPA, Lilacs and Scielo. Case reports addressing interruption of treatment due to any adverse event related to abatacept (ABA), adalimumab (ADA), anakinra (ANA), certolizumab pegol (CER), etanercept (ETA), golimumab (GOL), infliximab (IFX), rituximab (RTX), secukinumab (SEC), tocilizumab (TCZ), tofacitinib (TOF) or ustekinumab (UST) in rheumatoid arthritis patients were evaluated. Baseline data, patient profile, previous and current treatments, cause of discontinuation and information on reintroduction of treatment were extracted from the case reports. One hundred and fifty-four studies (154 patients) reported 162 discontinuations of rheumatoid arthritis treatment due to adverse events (ETA = 57; IFX = 46; ADA = 32; TCZ = 13; RTX = 5; ANA = 3; GOL = 2; ABA = 2; TOF = 1; CER = 1; SEC = 0 and UST = 0). The mean age of patients was 56 (± 12.1) years and 82% were female. Seventy-four adverse events were confirmed (related to used drug), and 138 were observed in patients using anti-TNF. The most common adverse events were infections (21%), skin disease (15%), autoimmune disease (13%) and hematological disorders (9%). Case reports are important in the detection of rare adverse events and should be considered in the choice of appropriate therapy for patients.

Liver function changes in rheumatoid arthritis patients treated with tofacitinib: systematic review / 中华风湿病学杂志

Objective To evaluate the effects of tofacitinib on liver function in rheumatoid arthritis (RA) patients.Methods Literature search was performed in databases including PubMed,Cochrane Library,China National Knowledge Infrastructure and Wanfang to identify randomized controlled trials about RA treated with tofacitinib.The retrieval time was up to August 2016.Meta-analysis was conducted by Revman 5.5 software.Results A total of 7 studies were included,involving 2 965 patients.The results of Meta-analysis revealed that the incidence of alanine transaminase (ALT)＞1 upper limit of normal (ULN) in patients receiving both 5 mg and 10 mg bid tofacitinib was significantly higher than placebo [5 mg bid tofacitinib:RR=1.48,95％CI (1.20,1.82),P=0.000 2;10 mg bid tofacitinib:RR=1.67,95％CI (1.37,2.05),P＜0.01];there was no significant difference in the incidence of ALT＞3 ULN [5 mg bid tofacitinib:RR=1.81,95％CI (0.57,5.79),P=0.32;10 mg bid tofacitinib:RR=1.36,95％CI (0.57,5.25),P=0.49];the incidence of aspartate transaminase (AST)＞1 ULN was significantly higher than placebo [5 mg bid tofacitinib:RR=1.59,95％CI (1.25,2.03),P=0.000 2;10 mg bid tofacitinib:RR=1.90,95％CI(1.50,2.40),P＜0.01],there was no significant difference in the incidence of AST＞3 ULN [5 mg bid tofacitinib:RR=1.17,95％CI (0.27,5.17),P=0.83;10 mg bid tofacitinib:RR=0.95,95％CI (0.26,3.44),P=0.94].Conclusion Tofacitinib slightly increases ALT and AST in patient with RA.Due to the limited sources and lack of domestic studies,more randomized controlled trials are still needed to verify the above conclusion.