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ObjectivesTo update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA).MethodsFollowing the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting.ResultsFive overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6–8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures.ConclusionsThe 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

ObjectiveA systematic literature review (SLR; 2009–2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations.MethodsTwo SLRs focused on clinical trials employing a treatment approach targeting a specific clinical outcome were performed. In addition to testing clinical, functional and/or structural changes as endpoints, comorbidities, cardiovascular risk, work productivity and education as well as patient self-assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane databases and Clinicaltrial.gov for the period between 2009 and 2012 and separately for the period of 2012 to May of 2014.ResultsOf 8442 citations retrieved in the two SLRs, 176 articles underwent full-text review. According to predefined inclusion/exclusion criteria, six articles were included of which five showed superiority of a targeted treatment approach aiming at least at low-disease activity versus routine care; in addition, publications providing supportive evidence were also incorporated that aside from expanding the evidence provided by the above six publications allowed concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care.ConclusionsThe current study expands the evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care.

ObjectivesTo characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world.MethodsCross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated.ResultsA total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%).ConclusionThese results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.

Immune-mediated inflammatory diseases, such as rheumatoid arthritis and spondyloarthritis, pose challenges due to recurrent flares and gaps in patient monitoring. Traditional health care models often fail to capture disease progression effectively. This study aimed to describes the structured cocreation of the IMIDoc platform, an interdisciplinary initiative aimed at improving patient monitoring, education, and health care provider decision-making. IMIDoc was cocreated through an interdisciplinary team involving clinical experts, biomedical engineers, and technical developers, using user-centered design principles. The development process included the identification of unmet clinical needs, user-centered app design, implementation of medication management features, patient data recording capabilities, and educational content. A 3-month feasibility and functionality testing was performed to evaluate the usability and technical performance of the apption. During the feasibility testing, 111 entries were logged for the patient mobile app, comprising 76 errors identified and corrected, 16 improvements addressing functionality, usability, and performance, and 10 evolutionary suggestions. The professional interface received 45 entries, identifying 40 errors and 5 evolutionary suggestions. Ten iterative updates significantly enhanced the user interface intuitiveness and medication reminder functionality, aligning the solution closely with clinical workflows and user needs. The IMIDoc platform, developed by a multidisciplinary cocreation methodology, shows potential to improve the management of immune-mediated inflammatory diseases ithrough enhanced communication and monitoring. A multicenter clinical study with 360 patients across 5 Spanish hospitals will further evaluate its impact.

IntroductionPatients with ankylosing spondylitis (AS) are burdened with symptoms impacting work productivity measured by presenteeism, absenteeism, overall work impairment, and activity impairment. Ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, has been demonstrated to improve disease signs and symptoms in two phase 3 trials of AS. This study investigated for 52 weeks the effect of ixekizumab treatment on work productivity in patients with active AS.MethodsCOAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomized, controlled trials investigating the efficacy of ixekizumab 80 mg every 4 weeks (Q4W) and every 2 weeks (Q2W) in patients with AS naïve to biologic disease-modifying antirheumatic drugs (bDMARDs; COAST-V) or who were inadequate responders or intolerant to tumor necrosis factor inhibitors (TNFi; COAST-W). Work productivity was measured with the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis at weeks 16 and 52. Absenteeism, presenteeism, and overall work impairment were assessed for patients reporting paid work. Activity impairment was assessed regardless of work status.ResultsAt baseline, 66.2% (434/656) of patients reported paid work. At week 16, bDMARD-naïve patients treated with both ixekizumab dose regimens and TNFi-experienced patients treated with ixekizumab Q2W reported significant improvements in activity impairment (p < 0.01 and p < 0.05, respectively). TNFi-experienced patients treated with ixekizumab showed significant improvements versus placebo in presenteeism and overall work impairment (p < 0.05); bDMARD-naïve patients had numeric improvements. After week 16, patients initially on placebo switched to ixekizumab and patients already treated with ixekizumab continued treatment. Improvements in work productivity and daily activity were sustained through week 52 for both bDMARD-experienced and -naïve patients.ConclusionBoth bDMARD-naïve and TNFi-experienced patients with AS had greater improvements in work productivity and activity impairment when receiving ixekizumab compared to placebo at week 16. Improvements in work productivity and activity impairment achieved at week 16 were sustained through week 52 with ixekizumab treatment.

There are two different approaches to involve participants in consecutive rounds of a Delphi survey: (1) invitation to every round independent of response to the previous round (“all-rounds”) and (2) invitation only when responded to the previous round (“respondents-only”). This study aimed to investigate the effect of invitation approach on the response rate and final outcome of a Delphi survey. Both experts (N = 188) and patients (N = 188) took part in a Delphi survey to update the core outcome set (COS) for axial spondyloarthritis. A study with 1:1 allocation to two experimental groups (ie, “all-rounds” [N = 187] and “respondents-only” [N = 189]) was built-in. The overall response rate was lower in the “respondents-only group” (46%) compared to the “all-rounds group” (61%). All domains that were selected for inclusion in the COS by the “respondents-only group” were also selected by the “all-rounds group.” Additionally, the four most important domains were identical between groups after the final round, with only minor differences in the other domains. Inviting panel members who missed a round to a subsequent round will lead to a better representation of opinions of the originally invited panel and reduces the chance of false consensus, while it does not influence the final outcome of the Delphi.

Biological therapies, such as TNF inhibitors (TNFi), are increasing remission (REM) rates in rheumatoid arthritis (RA) patients, although these are still limited. The aim of our study was to analyze changes in the profile of peripheral blood mononuclear cells (PBMC) in patients with RA treated with TNFi in relation to the clinical response. This is a prospective and observational study including 78 RA patients starting the first TNFi. PBMC were analyzed by flow cytometry both at baseline and at 6 months. Disease activity at the same time points was assessed by DAS28, establishing DAS28 ≤ 2.6 as the criteria for REM. Logistic regression models were employed to analyze the association between the changes in PBMC and REM. After 6 months of TNFi treatment, 37% patients achieved REM by DAS28. Patients who achieved REM showed a reduction in the percentage of naive B cells, but only when patients had received concomitant methotrexate (MTX) (OR: 0.59; 95% CI: 0.39–0.91). However, no association was found for patients who did not receive concomitant MTX (OR: 0.85; 95% CI: 0.63–1.16). In conclusion, PBMC, mainly the B-cell subsets, are modified in RA patients with TNFi who achieve clinical REM. A significant decrease in naive B-cell percentage is associated with achieving REM after 6 months of TNFi treatment in patients who received concomitant therapy with MTX.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4 + helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αβ) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

ObjectivesTo investigate the extent and performance of MRI lesions in the sacroiliac joint (MRI-SI) and spine (MRI-spine) in patients with suspected axial spondyloarthritis (axSpA).MethodsMRI-SI/spine of patients with chronic back pain (onset <45 years) in the SPondyloArthritis Caught Early (SPACE) cohort were scored by two well-trained readers for inflammation, fatty lesions, erosions, sclerosis/ankylosis and syndesmophytes. MRI performances were tested against the Assessment of Spondyloarthritis international Society (ASAS) axSpA criteria (positive: imaging-arm+ or clinical-arm+; negative: possible axSpA (few spondyloarthritis (SpA) features present) or no SpA). Arbitrary cut-off levels for MRI lesions were set to assure at least 95% specificity (tested in the no SpA group).ResultsIn total 126 patients were ASAS criteria positive (73 imaging-arm+ (22 by modified New York criteria (mNY)+; 51 by MRI+mNY−); 53 clinical-arm+) and 161 were ASAS criteria negative (89 possible axSpA and 72 no SpA). On MRI-SI (n=287), at least three fatty lesions (or at least three erosions) were seen in 45.5 (63.6)% of mNY+ patients, 15.7 (47.1)% of MRI+mNY− patients and 15.1 (13.2)% of clinical-arm+ patients versus 3.4 (6.7)% of possible axSpA patients and 2.8 (4.2)% of no SpA patients. A combined rule (at least five fatty lesions and/or erosions) performed equally well. Sclerosis and ankylosis were too rare to analyse. On MRI-spine (n=284), at least five inflammatory lesions (or at least five fatty lesions) were seen in 27.3 (18.2)% of mNY+ patients, 13.7 (21.6)% of MRI+mNY− patients and 3.8 (1.9)% of clinical-arm+ patients versus 4.5 (6.7)% of possible SpA patients and 2.9 (4.3)% of no SpA patients.ConclusionsThe presence of (1) at least five fatty lesions and/or erosions on MRI-SI, (2) at least five inflammatory lesions or (3) at least five fatty lesions on MRI-spine allows an acceptable discrimination of axSpA and no SpA, while assuring >95% specificity.

Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS. This post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16-48. nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1-6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points. 269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4-8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8-24 (12-40) weeks with tofacitinib vs. 24-32 weeks (32 weeks-not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment. Improvements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment. ClinicalTrials.gov, NCT03502616, 11 April 2018.