Beneficial effect of temporary methotrexate interruption on B and T cell responses upon SARS-CoV-2 vaccination in patients with rheumatoid arthritis or psoriatic arthritis.

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.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Real-World Treatment Patterns and Clinical Outcomes of Baricitinib in Rheumatoid Arthritis Patients in Spain: Results of a Multicenter, Observational Study in Routine Clinical Practice (The ORBIT-RA Study).

INTRODUCTION: Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved to treat rheumatoid arthritis (RA). This study aimed to investigate patients' characteristics, prescription patterns, effectiveness, and treatment persistence in patients receiving baricitinib in real-world practice in Spain. METHODS: This retrospective longitudinal cohort study conducted in five rheumatology units included adults with RA initiating baricitinib (Sep-2017-May-19) with at least a 6-month-follow-up. Demographic/clinical characteristics, prescription patterns, and changes in disease activity and pain level were collected until treatment discontinuation/end of follow-up. Treatment persistence was estimated by Kaplan-Meier methods. RESULTS: Data from 182 patients were included (mean (SD)): 83.5% women, 62.2 (12.3) years, body mass index 26.8 (5.1), disease duration 13.2 (10.8) years and Charlson Comorbidity Index score 2.4 (2.0). All patients had received at least one conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) before starting baricitinib and 78.0% at least one biologic disease-modifying anti-rheumatic drugs (bDMARD). Furthermore, 90.1% started with baricitinib 4 mg/day; 43.4% in monotherapy. One hundred and twelve (61.5%) of patients continued baricitinib at data collection time; mean persistence was 14.1 (0.5) months. Overall treatment persistence was 79.7/64.8/59.1% at 6/12/18 months. Seventy (38.5%) patients discontinued baricitinib during follow-up due to loss of efficacy (68.6%) or adverse events (18.6%). In those patients with available scores at the different observed cut-off points, remission or low disease activity was reported in 71.6 and 76.3% of patients at 6/12 months at any index: Disease Activity Score 28 joints using erythrocyte sedimentation rate (DAS28-ESR) (73.1 and 73.5%), Simplified Disease Activity Index (SDAI) (62.4 and 75.0%), and Clinical Disease Activity Index (CDAI) (66.7 and 78.1%). Good or moderate European League Against Rheumatism (EULAR)-response was noted in 80.0 and 78.2% of patients, respectively. Improvement from baseline in pain (Visual Analog Scale) was 2.5 cm and 3.0 cm at 6/12 months, respectively. CONCLUSIONS: This Spanish cohort of patients treated with baricitinib had a long-standing and refractory disease. Nevertheless, high persistence and improvements in disease activity and pain were found at 6 and 12 months after treatment initiation, independently of the composite disease activity measure used, reinforcing the effectiveness of baricitinib in routine clinical practice.

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons.

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.

Unmet needs in the management of cardiovascular risk in inflammatory joint diseases.

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.

Treatment of polymyalgia rheumatica.

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 12.5-25 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.

Tocilizumab for the treatment of adult-onset Still's disease.

INTRODUCTION: Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predominance of systemic symptoms and another manifested by progressive chronic polyarthritis. Glucocorticoids remain the mainstay in the treatment of AOSD. However, biologic therapies are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main retrospective and prospective studies, and case series on the use of the anti-interleukin (IL)-6 receptor tocilizumab in AOSD. Expert opinion: Since IL-6 serum levels are highly increased in both active systemic and polyarticular phenotypes, IL-6 blockade was considered to be a plausible therapeutic option for the management of AOSD. Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSD, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications. Nevertheless, there are some reports describing patients who are refractory to any therapy. Future research should focus on the identification of prognostic biomarkers that help us to tailor an individualized treatment for each type of patient and in the search of new disease activity indices that help us to monitor the response to the therapy more closely.