Discussion
cancers, tumor necrosis, RA, pain, deaths, vascular syndrome
CANCERS, TUMOR NECROSIS, EVENT, DIABETES MELLITUS, GCA, GIANT CELL ARTERITIS, CHRONIC INFLAMMATION, PMR, HYPERTENSION, PATHOGENESIS, INFLAMMATORY DISEASE
PMR is a classic inflammatory disease with an acute onset but an unknown cause. In the first cohort, we found that the patients with PMR had a significant inflammatory gene expression profile related to JAK signaling via RNA sequence analysis. Furthermore, tofacitinib suppressed the IL-6R and JAK2 expression of CD4As we know, patients with active PMR or RA both commonly suffer from severe pain. During clinical practice, NSAIDs are used to relieve pain for patients with RA. Tofacitinib usually works at week 2 in the treatment of RA. The NSAIDs were allowed in the tofacitinib group in the first 2 weeks and then were stopped. We can still consider the therapeutic effect of tofacitinib for PMR during the 24-week period. Furthermore, no severe side effects were found in the 24-week period of treatment of tofacitinib. We also found that the response rate was higher as expected in patients with PMR. We think tofacitinib may have a high response rate in the new diagnosed PMR patients who were naïve to glucocorticoid or biological agents. If we treat PMR patients who were relapsing on prior glucocorticoid or MTX or other agents in the real world, the expected response rate of tofacitinib may be not high.IL-6 is one of the key pro-inflammatory cytokines involved in the pathogenesis of PMR [S100A8 is an inflammatory mediator that can induce the JAK1/2-dependent signaling [As we know, glucocorticoids are the first-line drugs in the treatment of PMR. However, they come with numerous side effects. JAK1 and JAK3 were involved in the chronic inflammation of media and large arteries in an animal model of giant cell arteritis (GCA) [Here, we did an IIT study to explore whether single tofacitinib effectively treats new patients with PMR as glucocorticoid does. Excitingly, patients with PMR had a good response to tofacitinib therapy or steroid therapy in our study. We also collect the safety data of the drug after 24 weeks. No severe side effects or deaths were found in the 24-week period of treatment of tofacitinib. Recent ORAL surveillance study demonstrated that RA patients aged ≥50 years with ≥1 additional cardiovascular risk factor (for example, current cigarette smoker, hypertension, diabetes mellitus) have higher risks of major adverse cardiovascular event (MACE) and cancers during a median follow-up of 4.0 years, comparing the combined tofacitinib doses (5 or 10 mg twice daily) with tumor necrosis factor inhibitors (TNFis) [Our study has some limitations. The number of patients was small recruited from our medical center. We do not finish the functional experiment of candidate genes involved in the pathogenesis of PMR. PMR is closely associated with GCA, which is mainly an inflammatory vascular syndrome involving medium—and large—arteries. In most cases, PMR occurs in isolation but may be found in 40% to 60% of patients with GCA [