RESUMEN
Background: Acquired reactive perforating collagenosis (ARPC) poses a clinical challenge with an unclear pathogenesis. This disease has been frequently proven resistant to immunosuppressive treatments, significantly affecting the quality of life of patients. In this report, we highlight the efficacy of baricitinib as a viable option for maintenance therapy in ARPC. Case summary: An 81-year-old woman presented to our hospital with recurrent pruritus and cup-like ulcerated lesions on her trunk and limbs persisting for 1 year. She exhibited limited response to oral antihistamines and topical steroids. Past medical history revealed a prolonged history of coronary heart disease and type 2 diabetes spanning several years to decades. Histopathological examination revealed cup-shaped depressions filled with necrotic inflammatory debris. In the dermis, a mixed inflammatory infiltrate composed of lymphocytes and histiocytes was observed. Van Gieson staining indicated the elimination of fibrous tissue extending from the dermis into the epidermis. Consequently, a diagnosis of ARPC was established. Due to the inadequate response to conventional treatments and the severe itching, we initiated baricitinib therapy for ARPC, resulting in gradual symptom improvement. Follow-up assessments showed no adverse reactions and normal laboratory findings. Conclusion: The case report suggests that baricitinib might offer significant therapeutic benefits for ARPC.
Asunto(s)
Azetidinas , Enfermedades del Colágeno , Purinas , Pirazoles , Sulfonamidas , Humanos , Femenino , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Sulfonamidas/uso terapéutico , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Anciano de 80 o más Años , Purinas/uso terapéutico , Purinas/efectos adversos , Enfermedades del Colágeno/tratamiento farmacológico , Resultado del Tratamiento , Piel/patología , Piel/efectos de los fármacosRESUMEN
Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA.
Asunto(s)
Alopecia Areata , Inhibidores de las Cinasas Janus , Metaanálisis en Red , Humanos , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificación , Resultado del Tratamiento , Administración Oral , Purinas/administración & dosificación , Purinas/efectos adversos , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Índice de Severidad de la Enfermedad , PirazolesRESUMEN
BACKGROUND: Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. METHODS: We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. RESULTS: Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). CONCLUSIONS: In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.
Asunto(s)
Artritis Reumatoide , Azetidinas , Inhibidores de las Cinasas Janus , Piperidinas , Purinas , Pirazoles , Sulfonamidas , Humanos , Artritis Reumatoide/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Estudios Retrospectivos , Anciano , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Purinas/uso terapéutico , Purinas/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Triazoles/uso terapéutico , Triazoles/efectos adversos , Factores de Riesgo , Adulto , PiridinasRESUMEN
Patients with rheumatoid arthritis (RA) who receive immunosuppressive medications have a heightened risk of infection. The goal of our study was to calculate the pooled cumulative incidence and risk of infection in patients with RA treated with Janus kinase inhibitors (JAKi). The PubMed and EMBASE databases were queried for randomized controlled trials comparing patients with RA treated with JAKi (upadacitinib, baricitinib, tofacitinib, peficitinib, or filgotinib), defined as the treatment group, compared with control subjects, defined as participants receiving placebo or treatment regimen that was similar to that of participants in the treatment group, with the exception of JAKi. The primary study endpoint was the relative risk (RR) of any-grade and severe infection. The secondary endpoints were RR and cumulative incidence of opportunistic infections, herpes zoster, and pneumonia. The Stata v17 software was used for all data analysis. Results showed that treatment with baricitinib was associated with an increased risk of any-grade (RR 1.34; 95% CI: 1.19-1.52) and opportunistic (RR 2.69; 95% CI: 1.22-5.94) infection, whereas treatment with filgotinib (RR 1.21; 95% CI: 1.05-1.39), peficitinib (RR 1.40; 95% CI: 1.05-1.86) and upadacitinib (RR 1.30; 95% CI: 1.09-1.56) was associated with increased risk of any-grade infection only. Analysis based on type of infection showed a pooled cumulative incidence of 32.44% for any-grade infections, 2.02% for severe infections, 1.74% for opportunistic infections, 1.56% for herpes zoster, and 0.49% for pneumonia in patients treated with any JAKi during the follow-up period. Treatment with specific JAKi in patients with RA is associated with an increased risk of any-grade and opportunistic infections but not severe infection. Close clinical monitoring of patients with RA treated with JAKi is required to establish the long-term infection risk profile of these agents.
Asunto(s)
Artritis Reumatoide , Azetidinas , Inhibidores de las Cinasas Janus , Piperidinas , Purinas , Pirazoles , Pirimidinas , Sulfonamidas , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Humanos , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Incidencia , Purinas/efectos adversos , Purinas/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Herpes Zóster/epidemiología , Herpes Zóster/inducido químicamente , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/inducido químicamente , Pirroles/efectos adversos , Pirroles/uso terapéutico , Niacinamida/análogos & derivados , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Infecciones/epidemiología , Infecciones/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como Asunto , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Triazoles/efectos adversos , Triazoles/uso terapéutico , Adamantano/análogos & derivados , PiridinasRESUMEN
Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5 months versus 33.5 months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points ⢠An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. ⢠Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. ⢠The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.
Asunto(s)
Corticoesteroides , Artritis Reumatoide , Azetidinas , Herpes Zóster , Inhibidores de las Cinasas Janus , Humanos , Artritis Reumatoide/tratamiento farmacológico , Herpes Zóster/inducido químicamente , Herpes Zóster/prevención & control , Herpes Zóster/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Factores de Riesgo , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Piperidinas/administración & dosificación , Incidencia , Pirazoles/efectos adversos , Purinas/efectos adversos , Pirimidinas/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , COVID-19/epidemiología , Adulto , SARS-CoV-2 , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéuticoRESUMEN
An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period.
Asunto(s)
Alopecia Areata , Anticuerpos Monoclonales Humanizados , Azetidinas , Dermatitis Atópica , Purinas , Pirazoles , Sulfonamidas , Humanos , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Femenino , Purinas/administración & dosificación , Purinas/efectos adversos , Niño , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Pirazoles/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Quimioterapia CombinadaRESUMEN
The safety profile of baricitinib (BARI), a Janus kinase inhibitor broadly used for the treatment of rheumatoid arthritis (RA), includes asymptomatic laboratory abnormalities, such as an increase in creatine kinase (CK). Data from randomized controlled trials suggest that concomitant myalgia is rare in RA and does not lead to drug discontinuation. We describe the case of a 68-year-old Caucasian female with longstanding, multi-failure RA who started BARI and achieved disease remission. However, she developed a symptomatic CK increase, as well as a parallel increase in total cholesterol, low-density lipoprotein, and triglycerides. Dechallenge-rechallenge demonstrated a plausible relationship between the clinical/laboratory abnormalities and BARI. In fact, when the drug was withdrawn, CK returned to normal and myalgia disappeared, whereas symptoms returned and CK levels increased when BARI was restarted. BARI may be rarely associated with symptomatic CK elevation, and this may pose clinical challenges, particularly for patients with multi-failure RA who achieved good disease control with BARI but required drug discontinuation due to intolerance.
Asunto(s)
Artritis Reumatoide , Azetidinas , Creatina Quinasa , Purinas , Pirazoles , Sulfonamidas , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Femenino , Purinas/efectos adversos , Purinas/uso terapéutico , Anciano , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Creatina Quinasa/sangre , Mialgia/inducido químicamente , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversosRESUMEN
OBJECTIVE: This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA. METHODS: The databases CNKI, VIP, Wanfang, CBM, and PubMed, Embase, Cochrane Library and Web of Science were searched to identify relevant randomized controlled trials (RCTs), all from the time of database creation to April 2024. Screening, data extraction, and risk of bias assessment (using Review Manager-5.3 software) were independently performed by at least two authors. The network meta-analysis was conducted using R 4.1.3 software. PROSPERO registration number: CRD42022370444. RESULTS: Thirty-three RCTs included 15,961 patients The experimental groups involved six JAK inhibitors (filgotinib, tofacitinib, decernotinib, baricitinib, upadacitinib and peficitinib) and 12 interventions (different doses of the six JAK inhibitors), and the control group involved adalimumab (ADA) and placebo. Compared with placebo, all JAK inhibitors showed a significant increase in efficacy measures (ACR20/50/70). Compared with ADA, only tofacitinib, low-dose decernotinib, and high-dose peficitinib showed a significant increase in ACR20/50/70. Decernotinib ranked first in the SUCRA ranking of ACR20/50/70. In terms of safety indicators, only those differences between low-dose filgotinib and high-dose upadacitinib, low-dose tofacitinib and high-dose upadacitinib were statistically significant. Low-dose filgotinib ranked first in the SUCRA ranking with adverse events as safety indicators. Only the efficacy and safety of tofacitinib ranked higher among different SUCRA rankings. CONCLUSION: Six JAK inhibitors have better efficacy than placebo. The superior efficacy of decernotinib and safety of low-dose filgotinib can be found in the SUCRA. However, there are no significant differences in safety between the different JAK inhibitors. Head-to-head trials, directly comparing one against each other, are required to provide more certain evidence.
Asunto(s)
Artritis Reumatoide , Azetidinas , Teorema de Bayes , Inhibidores de las Cinasas Janus , Metaanálisis en Red , Piperidinas , Pirimidinas , Humanos , Artritis Reumatoide/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Purinas/uso terapéutico , Purinas/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Compuestos Heterocíclicos con 2 Anillos/uso terapéutico , Compuestos Heterocíclicos con 2 Anillos/efectos adversos , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Niacinamida/efectos adversos , Benzamidas/uso terapéutico , Benzamidas/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Triazoles/uso terapéutico , Triazoles/efectos adversos , Triazoles/administración & dosificación , Adamantano/análogos & derivados , Piridinas , Valina/análogos & derivadosRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce. METHODS: From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years. RESULTS: In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups. CONCLUSION: In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points ⢠Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages ⢠An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed ⢠No significant differences in infection incidence were found between tofacitinib and baricitinib.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Azetidinas , Inhibidores de las Cinasas Janus , Piperidinas , Purinas , Pirazoles , Pirimidinas , Sulfonamidas , Humanos , Masculino , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Femenino , Persona de Mediana Edad , Artritis Reumatoide/tratamiento farmacológico , Purinas/uso terapéutico , Purinas/efectos adversos , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Anciano , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Incidencia , Herpes Zóster/epidemiología , Herpes Zóster/inducido químicamente , Adulto , Infecciones/epidemiología , Infecciones/inducido químicamenteRESUMEN
BACKGROUND: Targeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is still a lack of evidence on the difference in the efficacy and safety of different targeted small-molecule drugs. Therefore, this study was conducted to assess the efficacy and safety of different targeted small-molecule drugs for SLE. METHODS: Randomized controlled trials (RCTs) on targeted small-molecule drugs in the treatment of SLE in PubMed, Web of Science, Embase, and Cochrane Library were systematically searched as of April 25, 2023. Risk of bias assessment was performed for included studies using the Cochrane's tool for evaluating the risk of bias. The primary outcome indicators were SRI-4 response, BICLA response, and adverse reaction. Because different doses and courses of treatment were used in the included studies, Bayesian network meta-regression was used to investigate the effect of different doses and courses of treatment on efficacy and safety. RESULTS: A total of 13 studies were included, involving 3,622 patients and 9 targeted small-molecule drugs. The results of network meta-analysis showed that, in terms of improving SRI-4, Deucravacitinib was significantly superior to that of Baricitinib (RR = 1.32, 95% CI (1.04, 1.68), P < 0.05). Deucravacitinib significantly outperformed the placebo in improving BICLA response (RR = 1.55, 95% CI (1.20, 2.02), P < 0.05). In terms of adverse reactions, targeted small-molecule drugs did not significantly increase the risk of adverse events as compared to placebo (P > 0.05). CONCLUSION: Based on the evidence obtained in this study, the differences in the efficacy of targeted small-molecule drugs were statistically significant as compared to placebo, but the difference in the safety was not statistically significant. The dose and the course of treatment had little impact on the effect of targeted small-molecule drugs. Deucravacitinib could significantly improve BICLA response and SRI-4 response without significantly increasing the risk of AEs. Therefore, Deucravacitinib is very likely to be the best intervention measure. Due to the small number of included studies, more high-quality clinical evidence is needed to further verify the efficacy and safety of targeted small-molecule drugs for SLE.
Asunto(s)
Lupus Eritematoso Sistémico , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Resultado del Tratamiento , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Purinas/uso terapéutico , Purinas/efectos adversos , Terapia Molecular Dirigida/métodos , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , PirazolesRESUMEN
OBJECTIVES: The ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited. METHODS: A retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model. RESULTS: We identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(±12) and 59.0(±13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97-2.25)], stroke [n = 973, adj.ROR=1.25 (1.16-1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13-1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17-1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00-1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged≤65 years. CONCLUSION: In this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect.
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Antirreumáticos , Artritis Reumatoide , Azetidinas , Enfermedades Cardiovasculares , Inhibidores de las Cinasas Janus , Farmacovigilancia , Piperidinas , Pirimidinas , Humanos , Artritis Reumatoide/tratamiento farmacológico , Inhibidores de las Cinasas Janus/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Antirreumáticos/efectos adversos , Estudios Retrospectivos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Azetidinas/efectos adversos , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Pirazoles/efectos adversos , Purinas/efectos adversos , Adulto , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Sistemas de Registro de Reacción Adversa a Medicamentos , Vigilancia de Productos Comercializados , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/epidemiologíaRESUMEN
OBJECTIVE: To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting. METHODS: Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression. RESULTS: A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients. CONCLUSION: Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
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Antirreumáticos , Artritis Reumatoide , Azetidinas , Purinas , Pirazoles , Sulfonamidas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Azetidinas/uso terapéutico , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Medición de Resultados Informados por el Paciente , Purinas/administración & dosificación , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Índice de Severidad de la Enfermedad , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Insuficiencia del Tratamiento , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Inhibidores del Factor de Necrosis Tumoral/efectos adversosRESUMEN
Siponimod is a sphingosine 1-phosphate receptor (S1P) modulator used to treat secondary progressive multiple sclerosis (SPMS). We report 3 SPMS patients treated with siponimod who developed new or worsening peripheral oedema soon after commencing treatment. In one case, peripheral oedema resulted in immobility. Siponimod-related peripheral oedema deserves wider recognition due to the potential for morbidity and over-investigation. Clinicians should assess for pre-existing oedema and coexisting conditions that may predispose to developing peripheral oedema prior to commencing siponimod.
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Azetidinas , Compuestos de Bencilo , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Humanos , Esclerosis Múltiple Crónica Progresiva/complicaciones , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Crónica Progresiva/inducido químicamente , Esclerosis Múltiple/inducido químicamente , Azetidinas/efectos adversos , Edema/inducido químicamenteRESUMEN
OBJECTIVES: This study aims to evaluate the efficacy and safety of JAK inhibitors (JAKi) in a monocentric cohort of adult patients with juvenile idiopathic arthritis (JIA). METHODS: Patients attending a rheumatology transition clinic were retrospectively included in case of: i) JIA diagnosis according to current classification criteria (1); ii) age ≥18 years and iii) treatment with JAKi for at least 3 months. RESULTS: Seventeen adult patients with JIA were treated with JAKi (as first JAKi, 9 patients (52.9%) received tofacitinib and 8 (47.1%) baricitinib). At 3 months after JAKi initiation, 8 patients (47%) achieved a response and 4 patients (23.5%) achieved disease remission (3 patients with baricitinib and 1 with tofacitinib, 37.5% vs. 16.7%, p=0.294). None of those with systemic JIA and enthesitis-related arthritis obtained remission; the remission rate at 3 months was higher, although not significantly, in the oligoarticular subset compared to the polyarticular subset (37.5% vs. 20%). Patients with ≤1 active joint involvement at JAKi start had a higher remission rate (50% vs. 22.2%). Subjects who achieved remission on JAKi had a significantly lower pre-treatment DAS28-CRP compared to those with still active disease (p=0.010, Mann-Whitney U=4). A pre-treatment DAS28-CRP <3.76 predicted response to JAKi with 100% sensitivity and 84.6% specificity (p=0.023). The remission rate was lower among patients who had been treated with ≥2 biological drugs before JAKi start (9% vs. 66.7%; p=0.05). One patient in concomitant treatment with leflunomide developed severe arterial hypertension. CONCLUSIONS: JAKi may represent an effective and safe treatment option for adult JIA patients with low/moderate disease activity, particularly in case of oligoarticular involvement.
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Artritis Juvenil , Azetidinas , Inhibidores de las Cinasas Janus , Piperidinas , Purinas , Pirazoles , Pirimidinas , Inducción de Remisión , Sulfonamidas , Humanos , Artritis Juvenil/tratamiento farmacológico , Estudios Retrospectivos , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Masculino , Femenino , Adulto , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Resultado del Tratamiento , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Adulto Joven , Sulfonamidas/uso terapéutico , Adolescente , Purinas/uso terapéutico , Purinas/efectos adversos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the treatment efficacy and safety of baricitinib in patients with refractory Takayasu arteritis (TAK). METHODS: We performed a prospective cohort study in which baricitinib 4 mg daily was prescribed to patients with refractory TAK, combined with oral glucocorticoids (GCs). RESULTS: 10 patients with refractory TAK were enrolled with a median age of 28 (IQR=22-37) years, median disease duration of 50 (IQR=24-65) months. The median dose of GCs was 10 (IQR=8.1-22.5) mg prednisone or equivalence dosage at baseline. At 6 months of baricitinib treatment, 6/10 (60%) patients had an overall treatment response. During an average follow-up of 15.3 (range 4-31) months, 4/10 (40%) patients maintained overall treatment response. 8/10 (80%) patients tapered or maintained the same dose of GCs with no change of the combined classical synthetic disease-modifying antirheumatic drugs. Two patients discontinued GCs at 18 and 24 months and were in continuous remission till the end of the study. One patient withdrew baricitinib due to liver dysfunction. CONCLUSION: Baricitinib 4 mg daily is effective for refractory TAK and is well tolerated.
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Azetidinas , Purinas , Pirazoles , Sulfonamidas , Arteritis de Takayasu , Humanos , Lactante , Preescolar , Estudios Prospectivos , Arteritis de Takayasu/diagnóstico , Arteritis de Takayasu/tratamiento farmacológico , Centros de Atención Terciaria , Azetidinas/efectos adversos , Glucocorticoides/uso terapéuticoAsunto(s)
Anticuerpos Monoclonales Humanizados , Azetidinas , Purinas , Pirazoles , Sulfonamidas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/tratamiento farmacológico , Dermatosis Facial/tratamiento farmacológico , Dermatosis Facial/inducido químicamente , Cuello/patología , Purinas/uso terapéutico , Purinas/efectos adversos , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long-term data on JAK inhibitors in AA. OBJECTIVES: To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy. METHODS: Integrated data from the BRAVE-AA1 and BRAVE-AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2-mg or 4-mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week-52 responders; 2-mg: N = 65; 4-mg: N = 129) and baricitinib 4-mg-treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week-52 mixed responders; N = 110). Week-104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation. RESULTS: Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase. CONCLUSIONS: Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week-52 mixed responders, illustrating that long-term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed.
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Alopecia Areata , Azetidinas , Inhibidores de las Cinasas Janus , Purinas , Sulfonamidas , Adulto , Humanos , Alopecia/tratamiento farmacológico , Alopecia Areata/tratamiento farmacológico , Azetidinas/efectos adversos , Inhibidores de las Cinasas Janus/efectos adversos , Pirazoles/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
Baricitinib is a Janus kinase inhibitor that has been approved by the US Food and Drugs Administration for the treatment of severe alopecia areata (AA) in adults. However, the clinical trials that demonstrated the efficacy of baricitinib in the treatment of severe AA did not include men aged > 60â years or women aged > 70â years. We retrospectively assessed the efficacy and safety of baricitinib in 14 patients aged ≥ 65â years with moderate-to-severe AA. After a mean (SD) duration of 18.5 (11.9) months, a 72% reduction in mean Severity of Alopecia Tool score from baseline was observed. Partial or complete eyebrow and eyelash hair was observed in 57% and 43% of patients, respectively. The adverse effects of baricitinib were mild. No cases of venous thromboembolism, major adverse cardiovascular events or malignancy were reported.
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Alopecia Areata , Azetidinas , Purinas , Pirazoles , Índice de Severidad de la Enfermedad , Sulfonamidas , Humanos , Azetidinas/uso terapéutico , Azetidinas/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Alopecia Areata/tratamiento farmacológico , Purinas/uso terapéutico , Purinas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Anciano de 80 o más AñosRESUMEN
Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders. This meta-analysis pooled the conflicting results from all published randomized controlled trials (RCTs) about the efficacy and safety of baricitinib in patients with systemic lupus erythematosus (SLE). We systemically searched four electronic databases. RCTs comparing baricitinib versus placebo were included. Our outcomes were pooled as the risk ratio (RR) in the random effects model. Our primary outcome was the proportion of patients who achieved a SLE Responder Index-4 (SRI-4) response. A total of three RCTs, comprising 1849 patients, were included. Baricitinib 4 mg was associated with a significantly higher proportion of patients who attained SRI-4 response at week 24 (RR = 1.19, 95% CI [1.05, 1.35], P < 0.01). However, this did not reach statistical significance with baricitinib 4 mg at week 52 and baricitinib 2 mg at both week 24 and week 52 (RR = 1.13, 95% CI [0.96, 1.34], P = 0.15; RR = 1.09, 95% CI [0.96, 1.24], P = 0.20; RR = 1.05, 95% CI [0.92, 1.19], P = 0.50, respectively). The risk for serious infections was higher in the baricitinib 4 mg group (RR = 2.23, 95% CI [1.13, 4.37], P = 0.02). Baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg might have the potential to reduce SLE disease activity; however, further research is required to evaluate its long-term efficacy. Until higher-quality evidence is developed, the benefits and risks of baricitinib should be considered before initiating its therapy. Key Points ⢠Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders; however, its efficacy in patients with systemic lupus erythematosus (SLE) is still inconclusive. ⢠In our meta-analysis, baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg significantly reduced SLE activity in terms of SRI-4 response at week 24. However, this did not reach statistical significance at week 52. ⢠Further studies are required to investigate the long-term efficacy of baricitinib 4 mg in patients with SLE.