RESUMEN
OBJECTIVES: To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05). RESULTS: We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64â weeks (range 15-161â weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)). CONCLUSIONS: Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Infecciones Oportunistas/inducido químicamente , Piperidinas/efectos adversos , Pirimidinas/efectos adversos , Pirroles/efectos adversos , Tuberculosis/inducido químicamente , Antirreumáticos/uso terapéutico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/inmunología , Ensayos Clínicos como Asunto , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Incidencia , Janus Quinasa 3/antagonistas & inhibidores , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/inmunología , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Medición de Riesgo , Tuberculosis/epidemiología , Tuberculosis/inmunologíaRESUMEN
OBJECTIVE: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. METHODS: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). RESULTS: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients' mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (-2.55[.30] vs. -2.52[.26]), HAQ-DI score (-.56[.07] vs. -.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (-2.37[.22] vs. -2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported. CONCLUSION: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs. CLINICAL TRIAL NUMBER: NCT03073109.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Humanos , Persona de Mediana Edad , Calidad de Vida , América Latina , Resultado del Tratamiento , Pirroles/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: The subjective complaints in patients with TBI (Traumatic Brain Injury) may persist for years. The most frequent complaints are headache, dizziness, drowsiness, mood disturbances, and memory and concentration disturbances. It is assumed that these complaints are caused by injury itself on one hand and psychological, emotional and motivation factors on the other. AIM: Evaluation of late posttraumatic complaints in patients with TBI more than a year after the trauma, and establishing their correlations to the severity of TBI and involvement in the lawsuits for financial compensation (litigation). MATERIALS AND METHODS: Ninety patients with the diagnosis of TBI were divided, according to the severity of the injury, in two groups: mild and with moderate-to-severe. The second classification criterion was litigation. A subjective complaints scale has been designed for the purpose of this research taking into consideration both anamnesis and hetero-anamnesis data. RESULTS: Cognitive disturbance, aggressiveness and sleep disturbance are more frequently reported by the subgroup of moderate-to-severe TBI patients, and they have not been related to the litigation. Posttraumatic headache (PTH) turned out to be a distinctive complaint regarding both classification criteria. Vegetative disturbances are significantly related to litigation, but not to the degree of injury. CONCLUSIONS: Predictive complaints reflecting the severity of TBI are memory deficit, concentration problems, and aggressiveness and sleep disturbance. Vegetative disturbances are predictive in relation to compensation claims. PTH is important from the forensic point of view for the patients with moderate to severe TBI.
Asunto(s)
Lesiones Encefálicas/complicaciones , Adolescente , Adulto , Anciano , Trastornos del Conocimiento/etiología , Femenino , Medicina Legal , Humanos , Masculino , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Cefalea Postraumática/etiología , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
OBJECTIVE: To evaluate work productivity of adult Latin American patients with rheumatoid arthritis (RA) treated with tofacitinib and biological disease-modifying anti-rheumatic drugs (bDMARDs) measured by the Work Productivity and Activity Impairment (WPAI) in RA questionnaire at 0- and 6-month follow-up. METHODS: This non-interventional study was performed in Colombia and Peru. Evaluated the effects of tofacitinib and bDMARDs in patients with RA after failure of conventional DMARDs. The WPAI-RA questionnaire was administered at baseline and at the 6-month (±1 month) follow-up. The results are expressed as least squares means (LSMs), and standard errors (SEs). RESULTS: One hundred patients treated with tofacitinib and 70 patients treated with bDMARDs were recruited. Twenty-eight percent of patients from the tofacitinib group and 40.0% from the bDMARDs group were working for pay at baseline. At month 6, the changes in absenteeism, presenteeism, and work impairment due to health were -18.3% (SE 7.7), -34.8% (SE 5.9), and -11.0% (SE 16.5), respectively, in the tofacitinib group and -19.4% (SE 8.0), -34.8% (SE 6.2), and -15.9% (SE 15.0), for the bDMARD group. CONCLUSION: For patients who reported working, there were improvements in presenteeism, absenteeism, and work impairment due to health in both groups. TRIAL REGISTRATION: NCT03073109.