Have Therapeutics Enhanced Our Knowledge of Axial Spondyloarthritis?

Purpose of Review An overview of how the treatment landscape of axial spondyloarthritis (axSpA) has shaped our understanding of the disease. Recent Findings Prior to the millennium, non-steroidal anti-inflammatory drugs (NSAIDs) were the only treatment for axSpA, yet only 30% of patients responded and many developed side effects. In 2003, the first biological disease-modifying drug (bDMARD) was licensed for axSpA which substantially improved outcomes in comparison to NSAIDs. In 2022, there are now several bDMARDs for axSpA; however, they too are not universally efficacious in treating axial inflammation and may have deleterious effects on extramusculoskeletal manifestations. Nevertheless, successful or not, each bDMARD gives invaluable insight into axSpA immunobiology. Summary This review discusses how much we have learned from the use of bDMARDs in axSpA, how this has redefined our understanding of the disease, and how we might use this knowledge to develop new and better treatments for axSpA in the future

Hidden in plain sight: is there a crucial role for enthesitis assessment in the treatment and monitoring of axial spondyloarthritis?

OBJECTIVE: To review the evidence surrounding the pathophysiology of enthesitis in axial spondyloarthritis (axSpA), its prevalence and contribution to the overall disease burden, and response to treatment at axial and peripheral sites. METHODS: Literature searches of the Cochrane Library, PubMed, and Embase / Medline using the terms “enthesitis“, “enthesopathy”, “spondyloarthritis”, “axial spondyloarthritis”, and “ankylosing spondylitis” were conducted. Publications mentioning enthesitis or enthesopathy in the context of pathophysiology, diagnosis, or treatment were included. RESULTS: Enthesitis is a common symptom of axSpA, occurring with high prevalence at axial and several peripheral sites. Inflammation at the site of enthesis is an early key manifestation of axSpA. Clinically evaluable enthesitis contributes significantly to the burden of disease, correlating with worse symptomatology and downstream structural damage. Despite its importance in driving axSpA disease processes, enthesitis is somewhat neglected in current approaches to disease assessment and management. Enthesitis is excluded from some commonly used disease activity measures, is not routinely assessed in clinical practice, and many methods of clinical assessment omit key accessible axial sites, such as the spinous processes. CONCLUSION: Enthesitis plays a central role in driving the pathophysiology of axSpA. There is a need for a renewed focus on the early detection, measurement and treatment of enthesitis

Early psoriatic arthritis: when is the right time to start advanced therapy?

Despite significant advances in the treatment of psoriatic arthritis (PsA) in the last two decades, remission remains elusive and there is no cure. Evidence from rheumatoid arthritis (RA) confirming enhanced response and outcome from earlier treatment intervention suggests the plausibility of the window of opportunity in the pathogenesis of RA. Yet, data are lacking in PsA. Although treatment response may be enhanced in shorter disease duration, it is unknown how this early intervention may impact long-term outcomes. Furthermore, it remains to be demonstrated whether there is a best treatment strategy and time of intervention. Crucially, the main hurdle when aiming for early treatment intervention is the ability to achieve a timely diagnosis that highlights the need to focus research efforts on characterizing the very early disease stages including the transition to PsA in the at-risk psoriasis population

Pointwise estimates for the Bergman kernel of the weighted Fock space

We prove upper pointwise estimates for the Bergman kernel of the weighted Fock space of entire functions in $L^2(e^{-2\phi})$ where $\phi$ is a subharmonic function with $\Delta \phi$ a doubling measure. We derive estimates for the canonical solution operator to the inhomogeneous Cauchy-Riemann equation and we characterize the compactness of this operator in terms of $\Delta \phi$

Recent advances in the management of psoriatic arthritis: practical considerations

Psoriatic arthritis (PsA) is an inflammatory arthritis characterized by inflammation of peripheral and / or axial joints, with or without other tissue manifestations, including skin psoriasis, dactylitis, enthesitis, uveitis, and inflammatory bowel disease. There has been an exponential increase in PsA treatment options over the last 2 decades, and while guidelines have attempted to keep up with the deluge of emerging data, there are several areas in which guidance remains sparse. This is, in part, due to a lack of robust strategy trials, head-to-head studies, and real-world observational data. In addition, trials seldom address key questions, such as the complex need to balance the treatment of joint disease with the other competing tissue manifestations of PsA, as well as other relevant medical comorbidities and patient lifestyle and personal preferences, all of which may change several times over the course of an individual’s lifetime. This article provides a concise summary of the current state of guidelines for the management of PsA, and an in-depth discussion of some of the areas where guidelines and evidence are still lacking. These areas of unmet clinical need in the treatment of PsA should be a priority for further PsA research in the coming years. Only by working with patients and addressing these gaps in our knowledge can we strive for a future where all PsA patients are able to receive treatment that is the best for them, and tailored to their specific needs at any particular time point in their disease trajectory

Increased Risk of Hypertension Associated with Spondyloarthritis Disease Duration: Results from the ASAS-COMOSPA Study

Objective: Spondyloarthritis (SpA) is associated with a number of cardiovascular (CV) comorbidities. We examined the association of SpA disease duration and delay in diagnosis with CV-related conditions. Methods: Using data from the COMOSPA study, the associations between SpA disease duration and CV-related conditions were evaluated in univariable and multivariable logistic regression models. Each model examined 1 CV-related factor as dependent and “SpA disease duration” as a predictor, adjusted for relevant confounders. Results: Data from 3923 subjects (median SpA disease duration 5.1 yrs, interquartile range 1.3–11.8 yrs) were available for analysis. The main CV-related conditions were hypertension (HTN; 22.4%), ischemic heart disease (2.6%), stroke (1.3%), and diabetes mellitus (5.5%). HTN was associated with SpA disease duration in both univariable and multivariable analysis, with an OR of 1.129 (95% CI 1.072–1.189; p < 0.001) for each 5-year increase in SpA disease duration. Other factors associated with HTN were age, male sex, current body mass index, ever steroid therapy, and ever synthetic disease-modifying antirheumatic drug therapy, but not nonsteroidal antiinflammatory drugs (NSAID). In subgroup analysis, the strongest association of HTN and disease duration was seen in subjects with the axial-only SpA phenotype (OR 1.202, 95% CI 1.053–1.372) but not in those with peripheral-only SpA (OR 0.902, 95% CI 0.760–1.070). The other CV conditions were not associated with SpA disease duration. Conclusion: Duration of SpA disease in the ASAS-COMOSPA cohort is associated with higher odds of HTN, particularly in those with axial disease, but not with other CV-related conditions. The association with HTN does not appear to be related to NSAID exposure