Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthritis: Pooled efficacy and safety analyses from Phase 3 and LTE studies.

OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. METHODS: Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. RESULTS: 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. CONCLUSIONS: In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population.

Current state of biosimilars in Mexico: The position of the Mexican College of Rheumatology, 2016. / Escenario actual de los medicamentos biocomparables en México: posicionamiento del Colegio Mexicano de Reumatología, 2016.

The present document is a position statement of the Mexican College of Rheumatology on the use of biosimilars in rheumatic diseases. This position considers that biosimilars should be considered as interchangeable, that automatic substitution without previous notice in stable patients during follow-up is not ethical, that the approval of a biosimilar should only be given after exhaustive review of preclinical and clinical data marked by Mexican regulations, that it should be clearly stated in the nomenclature of biologic drugs which is the innovator and which is the biosimilar, that it is not correct to choose a biosimilar as treatment based only on economic reasons or extrapolate indications based only on the approval of the innovator and in the absence of safety and efficacy data for the biosimilar.

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of Latin American patients with rheumatoid arthritis: Pooled efficacy and safety analyses of Phase 3 and long-term extension studies.

OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assessed tofacitinib efficacy and safety in the Latin American (LA) subpopulation of global Phase 3 and long-term extension (LTE) studies. MATERIALS AND METHODS: Data from LA patients with RA and inadequate response to disease-modifying antirheumatic drugs (DMARDs) were pooled across five Phase 3 studies. Phase 3 patients received tofacitinib 5 or 10mg twice daily (BID), adalimumab or placebo; patients in the single LTE study received tofacitinib 5 or 10mg BID; treatments were administered alone or with conventional synthetic DMARDs. Efficacy was reported up to 12 months (Phase 3) and 36 months (LTE) by American College of Rheumatology (ACR) 20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate [ESR]) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Incidence rates (IRs; patients with event/100 patient-years) of adverse events (AEs) of special interest were reported. RESULTS: The Phase 3 studies randomized 496 LA patients; the LTE study enrolled 756 LA patients from Phase 2 and Phase 3. In the Phase 3 studies, patients who received tofacitinib 5 and 10mg BID showed improvements vs placebo at Month 3 in ACR20 (68.9% and 75.7% vs 35.6%), ACR50 (45.8% and 49.7% vs 20.7%) and ACR70 (17.5% and 23.1% vs 6.9%) responses, mean change from baseline in HAQ-DI (-0.6 and -0.8 vs -0.3) and DAS28-4(ESR) score (-2.3 and -2.4 vs -1.4). The improvements were sustained up to Month 36 in the LTE study. In the Phase 3 studies, IRs with tofacitinib 5 and 10mg BID and placebo were 7.99, 6.57 and 9.84, respectively, for SAEs, and 3.87, 5.28 and 3.26 for discontinuation due to AEs. IRs of AEs of special interest in tofacitinib-treated LA patients were similar to the global population. CONCLUSION: In Phase 3 and LTE studies in LA patients with RA, tofacitinib demonstrated efficacy up to 36 months with a manageable safety profile up to 60 months, consistent with the overall tofacitinib study population.

Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis.

INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta. OBJECTIVE: The objective was to report outcomes of pregnancy cases identified through April 2014 from tofacitinib RA/psoriasis RCTs, RA post-approval non-interventional studies, and spontaneous adverse-event reporting. METHODS: Pregnancy outcomes were categorized as follows: healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or pending/lost to follow-up. RESULTS: Out of 9815 patients, 1821 female patients of child-bearing age were enrolled in the RA/psoriasis RCTs; 47 women became pregnant, including 33 who received tofacitinib monotherapy, 13 who received combination therapy with methotrexate (RA patients only), and one patient whose therapy was still blinded. No fetal deaths were reported. One congenital pulmonary valve stenosis (monotherapy, n = 1), seven spontaneous abortions (monotherapy, n = 4; combination therapy, n = 3), and eight medical terminations (monotherapy, n = 4; combination therapy, n = 3; blinded therapy, n = 1) were identified. Remaining cases reported healthy newborns (n = 25) or were pending/lost to follow-up (n = 6). Forty-four cases of paternal exposure to tofacitinib were reported (monotherapy, n = 43; combination therapy, n = 1), including five spontaneous abortions (monotherapy, n = 4; combination therapy, n = 1), 23 healthy newborns, and 16 pending/lost to follow-up. CONCLUSIONS: The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored.

Ectopic ACTH secretion (EAS) associated to a well-differentiated peritoneal mesothelioma: case report.

BACKGROUND: The association between mesotheliomas and ectopic ACTH secretion has been rarely reported; we present the first case of ectopic ACTH secretion (EAS) associated with a well-differentiated peritoneal mesothelioma in whom the high dose dexamethasone suppression test (HDDST) results and plasmatic ACTH levels were similar to those found in Cushing's disease (CD). CASE PRESENTATION: A 43-year-old hispanic woman with a 20 year history of treatment resistant diabetes mellitus and arterial hypertension. She had a full moon face, a buffalo hump, increased volume in both supraclavicular regions, purple striae in her arms and abdomen, truncal obesity, polymenorrhea and umbilical hernia. A cortisol suppression test with low dose dexamethasone (LDDST) with a result of 16.6 µg/dL and ACTH plasma levels were measured at 32.6 pg/mL. The high dose dexamethasone test suppression percentage was 84.8% and magnetic resonance imaging (MRI) showed no evidence of pituitary alterations, computed tomography (CT) showed images suggestive of uterine fibroid and an intra-abdominal tumor that correlated with an umbilical hernia, which reinforcement after contrast. Surgery was performed, finding uterine fibroids and paracolic tumor implants as well as on the omentum, bladder, bowel, ovaries and appendix. Pathology reported a well-differentiated peritoneal mesothelioma with positive immunohistochemistry for ACTH. CONCLUSIONS: Although most cases of ectopic secretion of ACTH derive from rapidly-developing lung tumors, with very high plasma ACTH levels and cortisol suppression percentages with high doses of dexamethasone under 60%, there is a small percentage of slow-developing, chronic tumors that are biochemically undistinguishable from Cushing's disease. Following the expert recommendations regarding imaging techniques it is possible to identify the associated tumor in most cases.

Linfoma angiocéntrico mediofacial simulando granulomatosis de Wegener limitada. Reporte de un caso / Midfacial angiocentric lymphoma simulting Wegener granulomatosis. A case report

Se reporta el caso de un paciente masculino de 21 años con lesiones granulomatosas en nariz y órbitas, quien tuvo síndrome febríl y pérdida de peso. Se sospechó el diagnóstico de Granulomatosis de Wegener limitada con base en el cuadro clínico y en los hallazgos de la biopsia. Sin embargo, por inmunotinción el diagnóstico definitivo fue de linfoma angiocéntrico mediofacial.