A systematic literature review of randomised controlled trials evaluating colchicine for cardiovascular prevention: There is an elephant in the room.

OBJECTIVES: To review randomised controlled trials (RCT) investigating colchicine (COL) for cardiovascular (CV) prevention in patients at high to very high CV risk aiming to extract data that could be useful in rheumatology practice. METHODS: A systematic search of multiple databases according to the PICO framework was performed from inception to April 3, 2023. Three researchers independently screened abstracts/titles and reviewed full texts reviewed. Data extraction was performed using a pilot-tested data extraction form. RESULTS: A total of 14,096 references were retrieved by the search and 30 articles, describing 28 RCTs, were included in the review (Total number of patients 16,795, of which 8,463 randomised to COL; dose 0.5-2 mg/day, treatment duration 1day-29 months). Only one of the 28 RCTs provided clear information on whether patients with rheumatic diseases (more specifically gout) were enrolled in the study cohorts and previous use of COL was an exclusion criterion only in 14 (50 %) RCTs. Previous therapy with glucocorticoids and/or non-steroidal anti-inflammatory drugs and/or immune suppressive therapies was an exclusion criterion only in 9 (32 %) RCTs. CONCLUSION: Our results highlight the need to redefine the eligibility criteria as well as the reporting of results in future RCTs in order to minimise bias or previous exposure to COL and also obtain data that could be useful in rheumatology practice.

Human Leukocyte Antigen B*27-Negative Spondyloarthritis: Clinical, Serological, and Radiological Features of a Single-Center Cohort.

The strong genetic association between HLA-B*27 and spondyloarthritis (SpA) accounts for about 90% of the susceptibility to axial SpA (axSpA), and the presence of HLA-B*27 is helpful in classifying patients according to the Assessment of SpondyloArthritis International Society (ASAS) classification criteria. However, over the years, other HLA-B alleles have been associated with an increased risk of developing SpA; on this basis, the aim of our study was to describe the demographic, clinical, and radiological characteristics of a cohort of SpA patients who were negative for HLA-B*27. We identified 85 patients with a clinical diagnosis of SpA displaying HLA-B alleles other than HLA-B*27; HLA-B*51 emerged as the most prevalent allele (N = 33, 39%), regardless of the fulfilment of either the axial or the peripheral ASAS criteria. The second most prevalent allele in the full cohort (N = 16, 19%) and in the patients fulfilling either the axial or the peripheral criteria was HLA-B*35. The third most prevalent allele in the full cohort was HLA-B*18 (N = 12, 15%), which was also the second most prevalent allele in the patients fulfilling neither of the two sets of criteria. Overall, the clinical picture was similar across the subgroups fulfilling the different sets of ASAS criteria; however, the patients not fulfilling any ASAS criteria had a higher likelihood of having arthritis compared to the patients fulfilling the axial criteria, whereas the Bath Ankylosing Spondylitis Functional Index was significantly higher in those patients fulfilling the axial criteria compared to those who did not fulfill any criteria. Our results indicate that other HLA alleles, beyond HLA-B*27, could be useful in facilitating SpA diagnosis, particularly in patients with a clinical picture which is consistent with SpA but does not fulfill the ASAS classification criteria.

Untangling the relationship between bempedoic acid and gout: results from a systematic literature review.

Background: Bempedoic acid (BA) is a small-molecule first-in-class of inhibitor of ATP citrate lyase that significantly lowers low-density lipoproteins cholesterol (LDL-c) in statin-intolerant and inadequate responders. Increased serum uric acid (SUA) levels and gout incidence have been described in BA-treated patients. The aim of this systematic review was to investigate the safety of BA regarding SUA levels and gout in randomised controlled trials (RCTs). Methods: A search on 7 databases was performed from inception to May 4, 2023. RCTs of BA monotherapy or combination with other lipid-lowering treatment (LLT) in patients with increased LDL-c were included. Dual data extraction was performed with disagreements resolved through consensus. Due to the methodological purpose of this review risk-of-bias assessment of studies was not performed. Results: 6 Phase 3 RCTs (N = 17,975 patients of which 9,635 received BA) 9 Phase 2 RCTs (N = 362 patients of which 170 received BA) and an open-label extension of a Phase 3 RCT were included. Gout and/or hyperuricemia were not mentioned as exclusion criteria, previous/current use of urate-lowering therapies (ULT) and/or colchicine and/or dietary patterns were not reported. Phase 3 RCTs: 2 studies specified the number of patients experiencing hyperuricemia over the study period (BA: 4.9%-11%; placebo: 1.9%-5.6%) and the effect size was significant only in 1 study (OR = 2.0, 95% CI 1.8-2.3). Four RCTs reported a higher incidence of gout in the BA arm however, when we calculated the effect size, it was small and often not significant. Two studies reported 0 cases of gout. The paucity of information about SUA levels at baseline and/or at the end of follow-up do not allow us to quantify the effect sizes for BA-induced SUA elevation. Data on gout from Phase 2 RCTs is scant. Conclusions: Data from phase 2 and 3 RCTs do not allow for confirming a clear association between BA and gout. It is conceivable that a careful assessment of SUA levels/history of gout at baseline and the concomitant use of urate-lowering agents may be instrumental to minimise the risk of new-onset gout/gout flares in patients treated with BA.

SpA plus IBD or IBD plus SpA: Does commutative property apply?

The term spondyloarthritis (SpA) encompasses a group of interrelated disorders characterised by the involvement of the musculoskeletal system as well as extra-articular manifestations like acute anterior uveitis, psoriasis and inflammatory bowel diseases (IBD). Likewise, IBD may present with various extra-intestinal manifestations among which those involving the musculoskeletal system, namely peripheral and axial SpA are the most common. The identification of patients with both SpA and IBD is of paramount importance in clinical practice since the coexistence of these two entities has been associated with great disability and decreased quality of life. In order to achieve an early diagnosis of IBD-SpA it is instrumental that rheumatologists seek for gastrointestinal symptoms in SpA patients and likewise that gastroenterologists seek for inflammatory musculoskeletal symptoms in patients with IBD. This narrative review aims at critically appraising the available evidence about SpA occurring in IBD patients versus IBD occurring in patients with SpA and at highlighting similarities and differences between the two scenarios.

Pathogenesis of rheumatoid arthritis: one year in review 2023.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by local and systemic inflammation. The complex interplay between immune cells and soluble mediators leads to the induction and perpetuation of aberrant inflammatory and autoimmune responses. The research carried out in the last year in the field of RA enabled the identification of new mechanisms involved in the pathogenesis of the disease and therefore unmasked new potential therapeutic targets. In this review article we summarised the new insights into RA pathogenesis from original research articles published in the last year.

The Interplay between Cardiovascular Risk, Cardiovascular Events, and Disease Activity in Primary Sjögren's Syndrome: Is Uric Acid the Missing Link?

(1) Background: Uric acid is a well-known cardiovascular (CV) risk factor in the general population but its role in the setting of rheumatic diseases other than gout is unclear. (2) Methods: This is a retrospective study investigating a cohort of 105 pSS patients recording clinical, serological, and CV-related variables including adherence to the Mediterranean diet. (3) Results: We observed a strong relationship between disease activity, interstitial lung disease (ILD), and CV events. The association between ILD and CV events was dependent on higher SUA levels but independent of other traditional CV risk factors. All three cases of previous non-fatal stroke were reported by females aged <65 years, with higher SUA levels, and two of them also had pSS-ILD. Forty (38%) patients had a 10-year risk of fatal and non-fatal CV disease events beyond the cut-off recommended for their age, and using the correction factor of 1.5 currently applied only to rheumatoid arthritis, we could better identify patient subsets characterized by different CV risk profiles including different SUA levels. (4) Conclusions: This study is the first to investigate in depth the role of SUA in the CV scenario of pSS. Our findings underpin the importance of assessing SUA levels in pSS in addition to the other traditional CV risk factors and to consider applying the correction factor for CV risk assessment tools to achieve a better stratification of CV risk.

Pathogenesis of rheumatoid arthritis: one year in review 2022.

The mechanisms underlying the pathogenesis of rheumatoid arthritis (RA) involve different components of the immune system. In subjects with genetic predisposition to develop RA, a tight interaction between cells and mediators of the innate and adaptive immune system leads to the amplification and perpetuation of inflammation and tissue remodelling. The research carried out in the last year in the field of RA has improved the current knowledge on the pathogenesis of the disease, and is potentially useful to develop new therapeutic approaches. Thus, in this review we provide an overview on the new insights into RA pathogenesis, resulting from a literature search of the data published in the last year.

Adherence to the Mediterranean diet and the impact on clinical features in primary Sjögren's syndrome.

OBJECTIVES: The relationship between dietary patterns, including the Mediterranean diet, and rheumatic and musculoskeletal diseases (RMDs) has been increasingly assessed but data on patients with established primary Sjögren's syndrome (pSS) is lacking. The aim of the study was to explore the adherence to the Mediterranean diet and its relationship with metabolic and inflammatory features in a cohort of patients with pSS. METHODS: Demographic, clinical and serological data, including anthropometric parameters and cardiovascular (CV) disease risk factors/events among others were collected from 91 pSS patients. Adherence to the Mediterranean diet over the previous 12 months was assessed with the 14-item PREvencion con DIeta MEDiterranea (PREDIMED) tool and the 28-item Mediterranean Lifestyle (MEDLIFE) index. RESULTS: According to the PREDIMED score 29 (31%) patients had a good adherence to the Mediterranean Diet, 57 (61%) a medium adherence and only 7 (8%) a poor adherence. No difference could be identified across groups with regard to demographic data, disease activity, CV risk factors or other parameters. With regard to the MEDLIFE, the total of blocks 1 and 2, that are related to Mediterranean foods and dietary habits, did not correlate with the total of block 3 (related to other healthy habits such as physical activity), meaning that the patients adhering the most to the Mediterranean Diet not necessarily had an overall healthy lifestyle. The PREDIMED score was inversely correlated with disease activity, as measured by ESSDAI (Spearman's rho=-0.27, p=0.009) and ClinESSDAI (Spearman's rho=-0.26, p=0.01). Fish consumption was associated with lower prevalence of hypertension. CONCLUSIONS: Adherence to the Mediterranean diet, with particular attention to fish consumption, may be beneficial on various domains in pSS, such as the CV system and the inflammatory environment, and as such should be recommended to patients with this disease.