RESUMO
B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA and PsA patients treated with MTX were recruited and randomly assigned to 3 groups: MTX-maintenance (n = 72), MTX-withdrawal for 1 week (n = 71) or MTX-withdrawal for 2 weeks (n = 73). Specific antibodies to several SARS-CoV-2 antigens and interferon (IFN)-γ and interleukin (IL)-21 responses were assessed. MTX withdrawal in patients without previous COVID-19 was associated with higher levels of anti-RBD IgG and neutralising antibodies, especially in the 2-week withdrawal group and with higher IFN-γ secretion upon stimulation with pools of SARS-CoV-2 S peptides. No increment of RA/PsA relapses was detected across groups. Our data indicate that two-week MTX interruption following COVID-19 vaccination in patients with RA or PsA improves humoral and cellular immune responses.
RESUMO
Osteoporosis has been classically considered a comorbidity of rheumatoid arthritis (RA). However, recent advances in the pathogenesis of osteoporosis in RA have shown a close interplay between cells of the immune system and those involved in bone remodeling, introducing new actors into the classic route in which osteoclast activation is related to the RANK/RANKL/OPG pathway. In fact, the inflammatory state in early stages of RA, mediated by interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α has the ability to activate and differentiate osteoclasts not only through their relationship with RANKL, but also through the Wnt/DKK1/sclerostin pathway, leading to bone loss. The role of synovial fibroblasts and activated T lymphocytes in the expression of the RANKL system and its connection to bone destruction is also depicted. In addition, autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are other pathogenic mechanisms for the development of bone erosions and systemic osteoporosis in RA, even before the onset of arthritis. The aim of this review is to unravel the relationship between different factors involved in the development of osteoporosis in RA patients, both the classic factors and the most novel, based on the relationship of autoantibodies with bone remodeling. Furthermore, we propose that bone mineral density measured by different techniques may be helpful as a biomarker of severity in early arthritis patients.
RESUMO
Polymyalgia rheumatica (PMR) is an inflammatory disease characterized by bilateral pain involving predominantly the shoulders and proximal aspects of the arms and less commonly the neck and the pelvic girdle. This review discusses briefly the main epidemiological data and clinical features of this condition. Especial attention is paid in the management of the disease. For this reason, both the classic management and the impact of new therapies are discussed in depth. In general, patients with PMR experience a rapid response to 12.5-25â¯mg/prednisone/day in less than a week. Patients with poor response to glucocorticoids or with relapsing disease require other therapies aimed mainly to spare glucocorticoids. Among them, methotrexate is the most commonly used. Nevertheless, different studies indicate that this agent yields only a modest effect. Biologic therapies against the main cytokines involved in the pathogenesis of the disease have been used in refractory patients. However, randomized controlled trials do not support the use of anti-tumor necrosis factor agents in PMR. In contrast, several case series and retrospective studies highlight the efficacy of the anti-interleukin-6 receptor tocilizumab in PMR. Nonetheless, controlled trials are needed to fully establish the beneficial effect of this agent. The potential favorable effect of the Janus-kinase inhibitors and new anti-interleukin-6 antagonists remains to be determined.