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Purpose of Review: To discuss the potential role of JAK inhibitors (JAKis) as a new therapeutic class for the treatment of axial spondyloarthritis (axSpA, including ankylosing spondylitis [AS] and non-radiographic axSpA [nr-axSpA])., Recent Findings: A phase III randomized controlled trial of tofacitinib (a "pan JAKi") in patients with active AS was found to be superior to placebo in achieving the ASAS20 primary endpoint at week 16 (56.4% and 29.4%, p < 0.0001, phase II trials of AS). Upadacitinib, a JAK1 inhibitor, has also been evaluated in a phase III trial for its efficacy and safety in AS. The primary endpoint, ASAS40 at week 16, was reached by 52% of the patients randomized to upadacitinib and 26% of the patients receiving placebo (p = 0·0003). All the important secondary endpoints also improved with both agents. No new changes in their safety profile were noted. However, the more frequent occurrence of cardiovascular and cancer adverse events associated with tofacitinib than with TNFi observed in the very recent post-marketing "ORAL surveillance" safety study, the results of which were released on January 27, 2021, may lead to safety concerns swirling around the whole class of JAKis. JAKis seem to be effective in treating signs and symptoms of AS but have not been studied in nr-axSpA. Both tofacitinib and upadacitinib have been pre-registered with the FDA for the treatment of AS. Upadacitinib has just recently received approval for this indication in the European Union..

Purpose of Review: To discuss the disease incidence and prevalence rates of axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS) relative to those of rheumatoid arthritis (RA)., Recent Findings: According to the most recently published systematic reviews, pooled prevalence estimates for RA are 0.38% in North America, and 0.21 to 0.25% in European subregions, while that of AS is 0.20% in North America and 0.25% in Europe. The estimated prevalence of axSpA has been reported to be approximately twice as common as AS in a study from the USA. This finding has also been supported by studies from northern Norway, central Italy, western Turkey, northern and southern regions of China, and rural Taiwan. These data suggest that axSpA, that encompasses AS, may be more prevalent than RA, at least in some countries. In general, higher occurrences of RA relative to AS have been noted worldwide, both in terms of incidence and prevalence. But axSpA, that encompasses AS, may be more prevalent than RA, at least in some countries. There is a need for concurrently run studies in the same population for a reliable comparison to establish occurrence of RA, AS, and axSpA. It is hoped that the implementation of the ICD-11 codes for axSpA will be helpful in determining a more accurate estimate of its incidence and prevalence.

Purpose of Review: This study aims to provide an update on current status of pharmacological therapies in early and advanced stages of axial spondyloarthritis (axSpA), as well as its late onset forms, and to discuss the need for treat to target strategies in this entity., Recent Findings: Efficacy of TNF inhibitors has been assessed in randomized controlled trials in axSpA, which included patients who had non-radiographic axSpA according to the ASAS classification criteria. The role of IL17/23 pathway as a therapeutic target in ankylosing spondylitis (AS) has been the focus of phase III studies of secukinumab (named MEASURE 1 and MEASURE 2) and a proof-of-concept study of ustekinumab. Potential efficacy of novel small molecules such as apremilast and tofacitinib has been explored in recent phase II trials. All the trials of TNF inhibitors in non-radiographic axSpA have achieved their primary endpoints, which resulted in their approval for this indication in Europe, but not in USA. The phase III trials of secukinumab have demonstrated significant therapeutic benefit as compared to placebo, resulting in its approval as the first non-TNF biologic for the treatment of AS, both by the US Food and Drug Administration and the European Medicines Agency.

Classification criteria should facilitate selection of similar patients for clinical and epidemiologic studies, therapeutic trials, and research on etiopathogenesis to enable comparison of results across studies from different centers. We critically appraise the validity and performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). It is still debatable whether all patients fulfilling these criteria should be considered as having true axSpA. Patients with radiographically evident disease by the ASAS criteria are not necessarily identical with ankylosing spondylitis (AS) as classified by the modified New York criteria. The complex multi-arm selection design of the ASAS criteria induces considerable heterogeneity among patients so classified, and applying them in settings with a low prevalence of axial spondyloarthritis (SpA) greatly increases the proportion of subjects falsely classified as suffering from axial SpA. One of the unmet needs in non-radiographic form of axial SpA is to have reliable markers that can identify individuals at risk for progression to AS and thereby facilitate early intervention trials designed to prevent such progression. We suggest needed improvements of the ASAS criteria for axSpA, as all criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances.

The new concept of axial spondylitis (axSpA) and the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axSpA have induced new clinical research that has broadened our understanding of spondyloarthritis (SpA) and has had indeed a positive impact on earlier diagnosis and treatment of patients with axSpA who have not yet developed radiographic sacroiliitis. The primary goal of any valid classification criteria for any disease is to provide a homogeneous study population with a common etiopathogenesis, similar prognosis, and similar response to identical treatment. Without such a homogeneous study population, robust clinical and basic science research in any subtype of SpA is not possible. All criteria are dynamic concepts that need updating as our knowledge advances and our review of the ASAS classification criteria of axSpA indicates that complex multi-selection design and unclear (not mutually exclusive) definitions of the imaging and clinical arms of the criteria results in patient heterogeneity across study populations. Therefore, there is a need to improve the validity of the ASAS criteria for axSpA. It is our opinion that in the meantime, the clinically well-established entity of AS, as defined by the modified New York (mNY) criteria, should be preserved for the most accurate comparison of the new research studies with those conducted over the last three decades, and that the use of the ASAS criteria should be restricted to patients with nr-axSpA, who are not recognized by the mNY criteria.

Familial Mediterranean fever (FMF) is characterized by recurrent, self-limited episodes of polyserositis, with articular involvement also being a common manifestation. The pattern and joint predilection of arthritis show many similarities to those of spondyloarthritis. Moreover, case series suggest an increased prevalence of ankylosing spondylitis or spondyloarthritis among FMF patients. FMF is caused by mutations in the MEFV gene encoding pyrin, which is believed to be involved in regulation of interelukin-1β activation. Recent studies conducted in populations with a high background carrier rate of MEFV variants have reported an increased frequency of M694V among AS patients with no personal or family history of FMF. These findings are of interest, as both candidate gene and genome-wide association studies suggest that the interleukin-1 cytokine pathway may be implicated in the pathogenesis of ankylosing spondylitis. Therefore, association of M694V with ankylosing spondylitis can be recognized as a geographic region-specific risk factor affecting a common inflammatory pathway in the disease pathogenesis.

The high-range estimate of 1.3% by the National Arthritis Data Workgroup for the prevalence of the entire spectrum of spondyloarthropathies (SpAs) suggests that SpAs may be more prevalent than rheumatoid arthritis (RA) in the United States. Recent surveys from many European countries using the same sample population have also found SpA to be at least as common as RA in most of the studied populations, including Finnish, Swedish, Lithuanian, French, Italian, and Turkish. Among Asian populations, China has the highest prevalence of SpA, with reported estimates generally higher than that of RA. In Thailand and Vietnam, the two diseases are probably equally common, whereas RA seems to be more prevalent than SpA in the rest of Asia, the Pacific Region, and Latin America, as indicated by studies following the COPCORD (Community-Oriented Program for the Control of Rheumatic Diseases) protocol. Both rheumatic disorders are rare in Africa, but SpA is less common than RA.