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Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations., Competing Interests: Declaration of competing interest TID: has nothing to disclose. FP: received grants and personal fees from Novartis, Eli Lilly, and UCB and personal fees from AbbVie, AMGEN, BMS, Celgene, Galapagos, Janssen, Hexal, Medscape, MSD, Pfizer and Roche outside the presented work. KG: received grants or contracts from Bristol Myers Squibb; received consulting fees from Abbvie, Lilly, Almirall, Janssen, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, and UCB; received payment /honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Abbvie Allergan Alimera Bayer Novartis Pfizer Roche Santen Thea; received support for attending meetings and/or travel from Abbvie, Almirall, BMS, and Lilly. UP: received grants or contracts from EU, BMBF; received consulting fees from Affibody, Alcon, Allergan, Janssen, Novartis, Panoptes, Pfizer, Roche, Thea, Lilly, Pfizer, Santen. Holds patents EP 19732357.9, PCT/EP2019/066419, PCT/J/2020–570,837.BS: received grants or contracts from Pfizer; received consulting fees from Abbvie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Endpoint Health, Falk Pharma, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, and Takeda; received payment /honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Abbvie, BMS, CED Service GmbH, Eli Lilly, Falk Pharma, Ferring, Galapagos, Janssen, Lilly, Pfizer, and Takeda.DP: received consulting fees from AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB; received payment /honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor)., Methods: Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated., Results: Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings., Conclusion: Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To evaluate the association of nociplastic (NoP) and neuropathic pain (NP) components with residual symptoms in patients with radiographic axial spondyloarthritis (r-axSpA) receiving biological disease-modifying antirheumatic drugs (bDMARDs)., Methods: 78 patients with r-axSpA from the GErman SPondyloarthritis Inception Cohort receiving a bDMARD for at least 3 months were included in this analysis. The Widespread Pain Index (WPI) and the PainDETECT (PD) questionnaire were used to quantify the NoP and the NP components, respectively. Axial Spondyloarthritis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were used as measures of residual symptoms. C reactive protein (CRP) was used as a measure of systemic inflammatory activity. Univariable and multivariable regression analyses of disease activity were performed. The regions of the WPI score and items of the PD score were used for cluster analyses., Results: Linear multivariable regression analysis showed that WPI and PD were independently associated with ASDAS (b=0.1, 95% CI 0.04 to 0.17, and b=0.05, 95% CI 0.02 to 0.08, respectively) and BASDAI (b=0.24, 95% CI 0.08 to 0.39, and b=0.17, 95% CI 0.1 to 0.25, respectively) in r-axSpA patients receiving stable treatment with bDMARDs. Furthermore, WPI and PD were found to be significantly associated with the presence of relevant residual symptoms as defined by BASDAI ≥4 (OR 1.93, 95% CI 1.09 to 4.15, and OR 1.32, 95% CI 1.04 to 1.85, respectively). The effects were present also in patients with normal level of CRP. Cluster analysis revealed three distinct pain distribution profiles and four specific sensory symptom constellations allowing differentiation of different pain subtypes., Conclusion: Both NoP and NP components seem to be associated with residual symptoms in patients with r-axSpA receiving treatment with bDMARDs., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with nonmusculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn's disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology., Methods: We performed 16S ribosomal RNA sequencing on stool samples of 277 patients (72 CD, 103 AAU, and 102 SpA) included in the German Spondyloarthritis Inception Cohort and 62 back pain controls without any inflammatory disorder. Discriminatory statistical methods were used to disentangle microbial disease signals from one another and a wide range of potential confounders. Patients were naive to or had not received treatment with biological disease-modifying antirheumatic drugs (DMARDs) for >3 months before enrollment, providing a better approximation of a true baseline disease signal., Results: We identified a shared, immune-mediated disease signal represented by low abundances of Lachnospiraceae taxa relative to controls, most notably Fusicatenibacter, which was most abundant in controls receiving nonsteroidal antiinflammatory drug monotherapy and implied to partially mediate higher serum C-reactive protein. Patients with SpA showed an enrichment of Collinsella, whereas human leukocyte antigen (HLA)-B27+ individuals displayed enriched Faecalibacterium. CD patients had higher abundances of a Ruminococcus taxon, and previous conventional/synthetic DMARD therapy was associated with increased Akkermansia., Conclusion: Our work supports the existence of a common gut dysbiosis in SpA and related inflammatory pathologies. We reveal shared and disease-specific microbial associations and suggest potential mediators of disease activity. Validation studies are needed to clarify the role of Fusicatenibacter in gut-joint inflammation, and metagenomic resolution is needed to understand the relationship between Faecalibacterium commensals and HLA-B27., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA)., Methods: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS., Results: The updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments., Conclusions: The selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials., Competing Interests: Competing interests: VN-C: grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer and UCB. ABoonen: grants from AbbVie ad Novartis and honoraria for boards or lectures form Abbvie, Galapagos and Lilly. PJM: research grants, consultation fees and/or speaker honoraria from Abbvie, Aclaris, Amgen, Bristol Myers, Boehringer-Ingelheim, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Lilly, Novartis, Pfizer, SUN Pharma and UCB. MD: consulting fees Pfizer, AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma. UK: grant and research support and consultancy fees from AbbVie, Amgen, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. RBML: honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli-Lilly, Novartis, Pfizer and UCB Pharma; Director of Rheumatology Consultancy BV. XB: consulting fees AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB. WB-M: research speaker's fees from Janssen, Lilly, Novartis, Pfizer and Biopas. PC: research grants/honoraria from Novartis, Pfizer, Zuellig Pharma and Janssen. LF: employee and shareholder of Pfizer. MG-C: research collaboration with and provides services to Novartis Pharma AG. LG: research grants/honoraria from AbbVie, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer and UCB. BKE: consultancy, research grants and speaker's fees from AbbVie, Amgen, BMS, Eva, Hekma, Janssen, Lilly, MSD, New Bridge, Novartis, Pfizer, Roche, Sanofi‐Aventis and Servier. NH: consultant for Amgen, Abbvie, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB. PMM: consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript. WM: consulting fees Abbvie, BMS, Boehringer, Celgene, Lilly, Janssen, Novartis, Pfizer and UCB; research and/or educational grants from Abbvie, Novartis and Pfizer; Chief Medical Officer CARE Arthritis Limited. AM: speaker honoraria for lectures, presentations from Abbvie, UCB, Novartis, Pfizer, Gilead, Janssen, MSD, BMS, Biogen and Lilly. NdP: employee of UCB Pharma. DP: research support from AbbVie, Lilly, MSD, Novartis and Pfizer, consulting fees from AbbVie, Biocad, Gilead, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer, Samsung Bioepis and UCB and speaker fees from AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer and UCB. MP: speaker honoraria for lectures, presentations from Novartis and UCB. SR: research grants from Galapagos, MSD, Novartis and Pfizer and consulting fees from AbbVie, Eli Lilly, MSD, Novartis, UCB and Sanofi. I-HS: employee of AbbVie, Immunology Clinical Development, USA. DvdH: consulting fees AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology bv. ABoel, HD, YHK and SvW: no competing interests to declare., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To summarize evidence on the relationship between early treatment (definition based on symptom/disease duration or radiographic damage) and treatment clinical response in patients with SpA., Methods: A systematic literature review was conducted in studies on SpA patients treated with NSAIDs or biological/targeted synthetic DMARDs addressing the impact of symptom/disease duration or presence of radiographic damage on treatment response assessed by any disease activity outcome. For categorical outcomes, relative risk, relative risk ratio and number needed to treat were calculated, and for continuous outcomes, differences in differences, to compare groups stratified based on symptom/disease duration or the presence of radiographic damage., Results: From the 8769 articles retrieved, 25 were included and 2 added by hand-search, all in axial SpA (axSpA), most of them with low risk of bias. Twenty-one studies compared groups based on symptom duration (n = 6) or disease duration (n = 15) and seven studies based on absence/presence of radiographic damage (two studies used two comparisons). When early axSpA was defined by symptom duration (<5 years) in randomized controlled trials, early treatment was associated with better outcomes in patients with non-radiographic axSpA [n = 2, ASAS40 relative risk ratio 5.24 (95% CI 1.12, 24.41) and 1.52 (0.60, 3.87)] but not in radiographic axSpA (n = 1) [ASAS20 0.96 (0.53-1.73)]. When early axSpA was defined based on disease duration or radiographic damage, no differences were found between groups., Conclusion: Evidence towards better outcomes in early axSpA is very limited and restricted to non-radiographic axSpA and <5 years symptom duration. When early axSpA is defined based on disease duration or radiographic damage, no differences in response to treatment are found., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Prior to surgical interventions physicians and patients with inflammatory rheumatic diseases remain concerned about interrupting or continuing anti-inflammatory medication. For this reason, the German Society for Rheumatology has updated its recommendations from 2014., Methods: After a systematic literature search including publications up to 31 August 2021, the recommendations on the use of of glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics (bDMARDs) were revised and recommendations on newer drugs and targeted synthetic (ts)DMARDs were added., Results: The glucocorticoid dose should be reduced to as low as possible 2-3 months before elective surgery (in any case <10 mg/day) but should be kept stable 1-2 weeks before and on the day of surgery. In many cases csDMARDs can be continued, exceptions being a reduction of high methotrexate doses to ≤15 mg/week and wash-out of leflunomide if there is a high risk of infection. Azathioprine, mycophenolate and ciclosporin should be paused 1-2 days prior to surgery. Under bDMARDs surgery can be scheduled for the end of each treatment interval. For major interventions Janus kinase (JAK) inhibitors should be paused for 3-4 days. Apremilast can be continued. If interruption is necessary, treatment should be restarted as soon as possible for all substances, depending on wound healing., Conclusion: Whether bDMARDs increase the perioperative risk of infection and the benefits and risks of discontinuation remain unclear based on the currently available evidence. To minimize the risk of a disease relapse under longer treatment pauses, in the updated recommendations the perioperative interruption of bDMARDs was reduced from at least two half-lives to one treatment interval., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA)., Methods: Following 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., Results: Five 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., Conclusions: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA., Competing Interests: Competing interests: SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly, and holds research grants from Pfizer and Lilly. AS has received speaker/consulting fees from UCB and Novartis. AO has nothing to declare. CW has nothing to declare. XB received consulting fees and research grants from AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. XB is an editorial board member of Annals of Rheumatic Diseases. RBML received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and UCB, and is director of Rheumatology Consultancy. FEVdB received consulting and/or speaker fees from AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. BB has nothing to declare. AB has nothing to declare. PC received consulting/speaker’s fees from Eli Lilly, Pfizer, AbbVie, Sanofi, Galapagos, Fresenius Kabi, Biogen, MSD, UCB and Novartis. AC received honoraria for lectures from AbbVie, Merck Sharp & Dohme and Novartis. FAvG received grants from Stichting ASAS, and consulting/speaker’s fees from Novartis, UCB, Pfizer, AbbVie, Eli Lilly, Bristol Myers Squibb and Celgene. PG received speaker’s fees from AbbVie. LG received consulting fees and research grants from AbbVie, Eli Lilly, Galapagos, Janssen, MoonLake, Novartis, Pfizer and UCB. JH has received speaker honoraria and participated in advisory boards for AbbVie, Lilly, Novartis and Janssen. MdH has nothing to declare. MH has received speaker’s fees from Novartis. UK has received grant and research support and consultancy fees from AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, Grünenthal, GSK, Janssen, MSD, Novartis, Pfizer, Roche and UCB. CL-M has received speaker/consulting fees from UCB, Novartis, Janssen, Eli Lilly, MSD and AbbVie. PMM has received honoraria from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, and UCB, and is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). HM-O received grants from Janssen, Novartis and UCB, and consultancy/speaker's fees from AbbVie, Biogen, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB. AM received research grants from UCB and consulting fees from AbbVie, Biogen, BMS, Eli Lilly, Gilead, Novartis, MSD, Pfizer and UCB. VN-C received grants/honoraria from AbbVie, Galapagos, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB. MJN received grant from Novartis and consultancy/speaker's fees from AbbVie, Eli Lilly, Janssen, Novartis and Pfizer. FMP-S received research grants from AbbVie, Janssen, and Novartis, and consulting fees from AbbVie, Bial, Biogen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Pharma Kern, UCB and Tecnimed. DP received research support from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer, and consulting fees from AbbVie, Biocad, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, MoonLake, Novartis, Pfizer, Samsung Bioepis, and UCB, and speaker's fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB. FP reports grants and personal fees from Novartis, Lilly and UCB, and personal fees from AbbVie, Amgen, BMS, Celgene, Janssen, Hexal, MSD, Pfizer and Roche. MR received consulting fees from AbbVie, Janssen, Eli Lilly, Novartis, Pfizer and UCB Pharma. MT has nothing to declare. SSZ has received consulting fees from UCB. NZ received research grants from AbbVie, Celgene, NewBridge and Pfizer; consulting fees from AbbVie, Eli Lilly, Pfizer, Gilead, Janssen, Novartis, NewBridge and Roche; and speaker's fees from AbbVie, Apotex, Eli Lilly, Janssen, Novartis, Pfizer, Pierre Fabre, Pharmaline, Roche and Sanofi-Aventis. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, and is director of Imaging Rheumatology., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prior to surgical interventions physicians and patients with inflammatory rheumatic diseases remain concerned about interrupting or continuing anti-inflammatory medication. For this reason, the German Society for Rheumatology has updated its recommendations from 2014., Methods: After a systematic literature search including publications up to 31 August 2021, the recommendations on the use of of glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics (bDMARDs) were revised and recommendations on newer drugs and targeted synthetic (ts)DMARDs were added., Results: The glucocorticoid dose should be reduced to as low as possible 2-3 months before elective surgery (in any case <10 mg/day) but should be kept stable 1-2 weeks before and on the day of surgery. In many cases csDMARDs can be continued, exceptions being a reduction of high methotrexate doses to ≤15 mg/week and wash-out of leflunomide if there is a high risk of infection. Azathioprine, mycophenolate and ciclosporin should be paused 1-2 days prior to surgery. Under bDMARDs surgery can be scheduled for the end of each treatment interval. For major interventions Janus kinase (JAK) inhibitors should be paused for 3-4 days. Apremilast can be continued. If interruption is necessary, treatment should be restarted as soon as possible for all substances, depending on wound healing., Conclusion: Whether bDMARDs increase the perioperative risk of infection and the benefits and risks of discontinuation remain unclear based on the currently available evidence. To minimize the risk of a disease relapse under longer treatment pauses, in the updated recommendations the perioperative interruption of bDMARDs was reduced from at least two half-lives to one treatment interval., (© 2021. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Psoriatic arthritis (PsA) is an inflammatory disease characterised by synovitis, enthesitis, dactylitis and axial involvement. The prevalence of axial involvement ranges from 25% to 70% in this patient group. Treatment recommendations for axial PsA were mainly extrapolated from guidelines for axial spondyloarthritis, and the main treatment options are non-steroidal anti-inflammatory drugs and biological disease-modifying antirheumatic drugs (tumour necrosis factor, IL-17 and IL-23 inhibitors). Tofacitinib was approved for the treatment of PsA and its efficacy on axial inflammation has been demonstrated in a phase II study of ankylosing spondylitis (AS). This prospective study aims to evaluate the efficacy of tofacitinib in reducing inflammation in the sacroiliac joints (SIJs) and spine on MRI in patients with axial disease of their PsA presenting with active axial involvement compatible with axial PsA., Methods and Analyses: This is a randomised, double-blind, placebo-controlled, multicentre clinical trial in patients with axial PsA who have evidence of axial involvement, active disease as defined by a Bath AS Disease Activity Index score of ≥4 and active inflammation on MRI of the SIJs and/or spine as assessed by and independent central reader. The study includes a 6-week screening period, a 24-week treatment period, which consist of a 12-week placebo-controlled double-blind treatment period followed by a 12-week active treatment period with tofacitinib for all participants, and a safety follow-up period of 4 weeks. At baseline, 80 subjects shall be randomised (1:1) to receive either tofacitinib or matching placebo for a 12-week double-blind treatment period. At week 12, an MRI of the whole spine and SIJs will be performed to evaluate the primary study endpoint., Ethics and Dissemination: The study will be performed according to the ethical principles of the Declaration of Helsinki and the German drug law. The independent ethics committees of each centre approved the ethical, scientific and medical appropriateness of the study before it was conducted., Trial Registration Number: NCT04062695; ClinicalTrials.gov and EudraCT No: 2018-004254-22; European Union Clinical Trials Register., Competing Interests: Competing interests: FP: research grants from Novartis; speaker and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche and UCB Pharma. MT: has nothing to disclose. BM: travel cost, speaker and/or consulting fees from Amgen, Bristol-Myers Squibb, Gilead, Sandoz Hexal and Stadapharm. VR-R: has nothing to disclose. MV: has nothing to disclose. DP: research grants from AbbVie, MSD, Novartis, and Pfizer; speaker and/or consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKlein, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, and UCB Pharma., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: We have now about 20 years of experience with the treatment of axial spondyloarthritis with biologics, which raises the question what we can learn from past experience, and which open questions should be addressed in future investigations., Recent Findings: Many studies have shown that axSpA patients - both patients in their nonradiological and radiological stage - respond similarly well to biologic treatment and these patients should be seen as having the same disease at different stages. AxSpA respond best to TNF-blocker - and probably also to other biologics - if the disease duration is short and if objective parameters of inflammation, such as C-reactive protein or MRI are positive. Primary aim of treatment is to reach and maintain clinical remission. Once remission is achieved, it can be maintained by continuing treatment, and in a proportion of yet not well defined patients the drug dose can be reduced without inducing a flare. The recent demonstration of a good efficacy, in addition to TNF blockers, also of IL-17 inhibitors and JAK-inhibitors in axSpA patients raises the question how to select the best patients for the best treatment. Radiographic progression can best be stopped by effectively suppressing inflammation, whether different drugs have here a different effect has still to be defined. More sensitive measurements of radiographic progression are urgently needed., Summary: Reaching and maintaining clinical remission and preventing structural bony damage is the primary treatment target in patients with axSpA. How to reach this aim best has to be further explored in the future., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To report the primary (1-year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA)., Methods: A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non-loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open-label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non-US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)-naive patients. Safety analyses included all patients who received ≥1 dose of study treatment., Results: Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open-label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi-naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). No new safety findings were reported., Conclusion: Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports., (© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: In patients with axial spondyloarthritis (axSpA), biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended to those with inadequate response or contraindications to non-steroidal anti-inflammatory drugs (NSAIDs). In case of failure of the first bDMARD, a switch within the class or to other bDMARD is recommended. Despite these treatment options, there is no optimal treat-to-target (T2T) strategy. This study aims to evaluate the efficacy of a T2T strategy in patients with axSpA, with secukinumab as a first-line bDMARD, compared with standard-of-care (SOC) treatment., Methods and Analyses: This is a randomised, parallel-group, open-label, multicentre ongoing study in patients with axSpA who are naïve to bDMARD and who have had an inadequate response to NSAIDs. The study will include an 8-week screening period, a 36-week treatment period and a 20-week safety follow-up period. At baseline, patients will be randomised (1:1) to T2T or SOC group. In the T2T group, patients will be treated with secukinumab 150 mg subcutaneous (s.c.) weekly until week 4 and then at week 8. For non-responders (patients without Ankylosing Spondylitis Disease Activity Score [ASDAS] clinically important improvement; change from baseline ≥1.1) at week 12, dose will be escalated to 300 mg s.c. every 4 weeks until week 24. Non-responders at week 24 will be switched to adalimumab biosimilar 40 mg s.c. every 2 weeks until week 34. In the SOC group, patients will receive treatment at the discretion of the physician. The primary endpoint is the proportion of patients achieving an Assessment in SpondyloArthritis International Society 40% (ASAS40) response at week 24., Ethics and Dissemination: The study is being conducted as per the ethical principles of the Declaration of Helsinki and after approval from independent ethics committees/institutional review boards. The first results are expected to be published in early 2022., Trial Registration Number: This study is registered with ClinicalTrials.gov, NCT03906136., Competing Interests: Competing interests: DP reports grants and personal fees from Abbvie, Eli Lilly, MSD, Novartis, and Pfizer, personal fees from Roche, BMS, UCB, and Celgene, outside the submitted work. XB reports consulting fees, research or institutional support and educational grants from AbbVie, BMS, Celgene, Chugai, Galapagos, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, Sanofi and UCB. LH has no conflicts of interest to disclose. MH, JV and CJ are employees of Novartis Pharma GmbH., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tumour necrosis factor-alpha inhibitors (TNFi) are an effective but expensive treatment option in axial spondylarthritis (axSpA) patients who fail to achieve disease control under conventional treatment., Objective: The aim of this study was to assess the cost of illness in axSpA patients treated with and without TNFi., Methods: Using German health insurance data, patients with axSpA who newly received TNFi between 2011 and 2015 were identified and matched by age and sex to a reference group of patients with axSpA without TNFi treatment. Costs for services performed in an outpatient setting, inpatient care, pharmacotherapy and for productivity loss due to absence from paid work were analyzed over a 2-year period. In patients treated with TNFi , the 2‑year period included 1 year before and 1 year after the initiation of TNFi., Results: Data from 1455 axSpA patients who received TNFi treatment were included in the analyses. Costs for services performed in an outpatient setting, inpatient care, pharmacotherapy (excluding TNFi) as well as productivity loss significantly decreased after initiation of TNFi. Mean total costs increased from € 6075 in the year prior to TNFi initiation to € 27,871 in the year after TNFi initiation. Excluding costs for TNFi, total costs decreased by 22% to € 4761. Mean total costs among the reference group of 1455 age and sex-matched axSpA patients who did not receive TNFi remained stable over 2 years: € 3939 in the first year vs. € 3832 in the second year., Conclusion: Initiation of TNFi treatment led to a sharp increase in the total costs of axSpA patients. Part of this increase was offset by a decrease of costs for services performed in an outpatient setting, inpatient care, pharmacotherapy (excluding TNFi) as well as productivity loss. In patients who did not receive TNFi, the costs remained stable over 2 years.

The cytokines IL-23 and IL-17 have an important role in the pathogenesis of, and as a therapeutic target in, both animal models of chronic inflammation and some human chronic inflammatory diseases. The traditional view is that a main source of IL-17 is T cells and that IL-17 production is under the control of IL-23. IL-17 inhibition has shown good efficacy in clinical trials for ankylosing spondylitis (AS), a subtype of axial spondyloarthritis (axSpA) characterized by radiographic evidence of sacroiliitis. On the basis of data from animal models, genetic studies and the investigation of tissue and blood samples from patients with AS, IL-23 had also been predicted to be important in the pathogenesis of this disease and was therefore considered a potential therapeutic target for axSpA. However, two placebo-controlled, double-blind clinical trials in axSpA of monoclonal antibodies directed against either the p40 protein or the p19 protein of the IL-23 molecule had clear negative results. These findings indicate that IL-23 and IL-17 are at least partly uncoupled in axSpA. Reasons as to why, when and how such an uncoupling might occur are discussed in this Review, with special reference to the unique microenvironment of the subchondral bone marrow in axSpA.

Purpose of Review: There was a substantial progress in the field of spondyloarthritis (SpA) in terms of understanding disease mechanisms, early diagnosis, and improved treatment. Nonetheless, several unresolved questions and unmet needs do remain., Recent Findings: Although the diagnostic delay in axial SpA is decreasing, it remains one of the longest in rheumatology. Application of referral strategies, as well as correct application and interpretation of imaging finding in the clinical context, is the main key to early diagnosis of axial SpA. Tumor necrosis factor (TNF) alpha and interleukin (IL)-17 represent currently two major treatment targets in SpA, while other promising targets such as IL-23 or IL-6 failed in clinical trials. There is an unmet need for strategy trials to optimize and to individualize treatment in SpA. The role of Janus kinases and their blockade in SpA is still to be explored. TNF blockade showed efficacy in peripheral SpA, and other targets (IL-17 and IL-23) should be investigated in clinical trials. Early, effective, and long-term suppression of inflammation is currently the best method to prevent structural damage progression in the spine in axial SpA, while specific effects of IL-17 blockade and of nonsteroidal anti-inflammatory drugs on new bone formation are still being investigated. This review summarizes the recent advances in diagnosis and treatment of SpA and discusses the current unmet needs in the field.

Objective: To evaluate the effect of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis., Methods: Patients opting to enrol had completed 2 years' treatment in the MEASURE 1 core study with subcutaneous secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from secukinumab 75-150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated., Results: Among 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators; n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline < 2) was observed in 79% of patients receiving either secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn's disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals., Conclusion: Through 4 years, secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile., Trial Registration: NCT01863732., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi)., Methods: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed., Results: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging-evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group)., Conclusion: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo., (© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

The management of spondyloarthritis (SpA) has substantially changed as a consequence of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). However, the treatment options in patients with axial SpA (axSpA) not responding to nonsteroidal anti-inflammatory drugs (NSAIDs) had been restricted to tumor necrosis factor alpha (TNFα) inhibitors for almost 15 years. With the approval of secukinumab, an interleukin (IL)-17A inhibitor, there is a new alternative in the treatment of axial SpA. In patients with psoriatic arthritis (PsA) not responding to conventional therapy with NSAIDs and conventional synthetic DMARDs, therapeutic options are more diverse. In addition to TNFα inhibitors and secukinumab, another IL-17A inhibitor ixekizumab, IL-12/23 blocker ustekinumab, phosphodiesterase-4 inhibitor apremilast, T-cell-mediated pathway inhibitor abatacept, and Janus kinase (JAK) inhibitor tofacitinib are the approved treatment. Nevertheless, there is still an unmet need for further treatment options in both axSpA and PsA. Further therapeutics, such as the dual IL-17A and F inhibitor bimekizumab, IL-17 receptor blocker brodalumab, and JAK inhibitors baricitinib, filgotinib and upadacitinib are in development for these indications. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab are further emerging drugs for PsA. Thus, the number of treatment options in SpA is likely to be increased over the next few years that make identification of optimal treatment strategies essential., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: The treatment of axial spondyloarthritis(axSpA) has been for nearly 15 years constricted to non-steroidal antirheumatic drugs and TNFα inhibitors. With the approval of secukinumab, a drug targeting the interleukin(IL)-17 axis became available. Nonetheless, an unmet need for further emerging therapeutic options remains. Areas covered: This review summarizes the recent and ongoing clinical trials with novel drugs in axSpA. Besides secukinumab, further therapeutics directed against the IL-17A (e.g. ixekizumab) as well as the dual IL-17A and F inhibitor bimekizumab and the IL-17RA antibody brodalumab are in development. Furthermore, several drugs targeting the IL-12/-23 axis are being evaluated. Pan-JAK and JAK-1 inhibitors might offer another effective mode of action. Expert opinion: The number of treatment options in axSpA is likely to be further extended in the coming years. Data of ongoing studies are needed to prove the efficacy of drugs directed against the IL-12/-23 axis as well as of JAK inhibition, whilst targeting the IL-17 axis was shown to be as effective as TNF inhibition by indirect comparison. There is an emerging need for trials aiming at identification of optimal treatment strategies in the scope of the treat-to-target concept in axSpA.

Objective: The aim of the study was to investigate the effect of radiographic spinal progression and disease activity on function and spinal mobility in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor-α (TNF-α) inhibitors for up to 10 years., Methods: Patients with AS who participated in 2 longterm open-label extensions of clinical trials with TNF-α inhibitors (43 receiving infliximab and 17 receiving etanercept) were included in this analysis based on the availability of spinal radiographs performed at baseline and at a later timepoint (yr 2, 4, 6, 8, and 10) during followup. Spinal radiographs were scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Function was assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI), spinal mobility by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and disease activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)., Results: After the initial improvement, BASFI and BASMI remained remarkably stable at low levels over up to 10 years despite radiographic spinal progression. In the generalized mixed effects model analysis, no association between the mSASSS and the BASFI change (β = 0.0, 95% CI -0.03 to 0.03) was found, while there was some effect of mSASSS changes on BASMI changes over time (β = 0.05, 95% CI 0.01-0.09). BASDAI showed a strong association with function (β = 0.64, 95% CI 0.54-0.73) and to a lesser extent, with spinal mobility (β = 0.14, 95% CI 0.01-0.26)., Conclusion: Functional status and spinal mobility of patients with established AS remained stable during longterm anti-TNF-α therapy despite radiographic progression. This indicates that reduction and continuous control of inflammation might be able to outweigh the functional effect of structural damage progression in AS.

Objective: To investigate the course of active inflammatory and fatty lesions seen on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (SpA) treated with the tumor necrosis factor (TNF) inhibitor infliximab added to naproxen as compared to those treated with naproxen alone., Methods: A total of 158 patients with active axial SpA were randomized (2:1) to receive 28 weeks of treatment with either infliximab 5 mg/kg plus naproxen 1,000 mg/day or placebo plus naproxen 1,000 mg/day. MRI of the sacroiliac (SI) joints and of the spine was performed at baseline and week 28. Images were scored for active inflammation and for fatty lesions., Results: After 28 weeks, there was a significant reduction of inflammation in the spine and in the SI joints in both treatment groups, which was, however, more prominent in the infliximab plus naproxen group (mean ± SD spine osteitis change score -2.9 ± 5.1, versus -2.0 ± 4.2 in the placebo plus naproxen group [P < 0.001]; SI joint osteitis change score -4.3 ± 5.2 in the infliximab plus naproxen group versus -3.9 ± 3.7 in the placebo plus naproxen group [P = 0.003]). Similarly, there was a significant increase in the fatty lesion score after 28 weeks in both groups; this change did not, however, differ significantly between groups (spine fatty lesion change score 0.8 ± 1.7 in the infliximab plus naproxen group versus 1.0 ± 1.8 in the placebo plus naproxen group [P = 0.72]; SI joint fatty lesion change score 1.7 ± 2.7 in the infliximab plus naproxen group versus 1.4 ± 2.6 in the placebo plus naproxen group [P = 0.86])., Conclusion: These findings indicate that effective antiinflammatory treatment of axial SpA is associated with an increase in fatty lesion scores, independent of concomitant treatment with or without anti-TNF., (© 2016, American College of Rheumatology.)

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for patients with symptomatic axial spondyloarthritis (SpA), who seem to respond best if treated early in the course of disease. The effect of NSAIDs on radiographic disease progression is less clear. Conventional disease-modifying antirheumatic drugs (DMARDs) are not recommended in the treatment of axial SpA, either alone or in combination with TNF blockers. Patients with nonradiographic axial SpA (nr-axSpA) seem to respond as well to TNF blockers as do patients with radiographic axial SpA (ankylosing spondylitis (AS)). However, patients with nr-axSpA should, in addition to a high severity of symptoms, also have objective signs of inflammation, detectable by MRI or by C-reactive protein testing, to be treated with TNF blockers. Whether early TNF-blocker treatment can retard new bone formation needs clarification. In clinical trials, anti-IL-17 agents and TNF blockers showed similar efficacy in patients with AS. The potential of IL-23 blockade for treatment of axial SpA needs to be further investigated. Treatment options for peripheral SpA have been much less thoroughly investigated than those for axial SpA. However, some data indicate that TNF blockers are effective for treating peripheral arthritis, enthesitis and dactylitis, the typical manifestations of peripheral SpA.

Objective: To investigate changes in magnetic resonance imaging (MRI)-assessed inflammation and structural lesions in the sacroiliac (SI) joints during treatment with adalimumab versus placebo., Methods: In a 48-week double-blind, placebo-controlled trial, 52 patients with spondyloarthritis were randomized to receive subcutaneous injections of either adalimumab 40 mg (n = 25) or placebo (n = 27) every other week for 12 weeks. Patients in the adalimumab group continued to receive and patients in the placebo group were switched to adalimumab 40 mg every other week for an additional 12 weeks. MRI of the SI joints was performed at weeks 0, 12, 24, and 48, and the images were assessed independently in a blinded manner using the modified Berlin and the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores for inflammation and structural lesions of the SI joints., Results: At baseline, 56% of the adalimumab group and ∼72% of the placebo group had an MRI-assessed inflammation score of ≥1. Among the patients with inflammation at baseline, the mean percent reductions in MRI scores for inflammation from week 0 to 12 were greater in the adalimumab group compared with the placebo group (Berlin method, -62% versus -5%; SPARCC method, -58% versus -12% [both P < 0.04]). Furthermore, the mean SPARCC erosion score decreased (-0.6) and the SPARCC backfill score increased (+0.8) in the adalimumab group from week 0 to week 12. From week 12 to week 24, larger absolute reductions in the Berlin/SPARCC inflammation scores and the SPARCC erosion score and larger increases in the Berlin/SPARCC fatty lesion scores were seen in the placebo group compared with the adalimumab group. In univariate regression analyses (analysis of covariance) and multivariate stepwise regression analyses, treatment with adalimumab was independently associated with regression of the SPARCC erosion score from week 0 to 12 but not with changes in the other types of MRI lesions., Conclusion: Significant changes in the Berlin and SPARCC MRI-assessed inflammation scores and in the SPARCC MRI-assessed erosion scores occurred within 12 weeks after initiation of adalimumab. Tumor necrosis factor inhibitor treatment was associated with resolution of erosions and the development of backfill., (© 2016, American College of Rheumatology.)

Objective: The aim of this study was to assess the degree of fluctuation of osteitis on MRI during long-term treatment with etanercept (ETN) in patients with early axial SpA (axSpA) with active inflammation (osteitis) on whole-body MRI in the spine and/or the SI joints at baseline., Methods: We analysed MRI data from 328 SI joint quadrants and 943 spine vertebral units (VUs) in terms of osteitis in the pooled data set of 41 patients who were treated with ETN for 3 consecutive years. Scoring was performed by two blinded radiologists at baseline, year 2 and year 3., Results: Through years 2 and 3, osteitis on MRI resolved completely in 56 of 144 (38.9%) SI joint quadrants and in 20 of 40 (50%) VUs affected at baseline, while persistent osteitis was found in 24 of 144 (16.7%) SI joint quadrants and in 8 of 40 (20.0%) spine VUs. The development of new osteitis in sites that were free of osteitis at baseline only occurred in 2 of 131 (1.5%) SI joint quadrants and in 3 of 862 (0.4%) spine VUs in both year 2 and year 3., Conclusion: There was a consistently small amount of osteitis on MRI in patients with early axSpA compared with baseline values, and only a very low rate of new-onset osteitis was found during 3 years of continuous treatment with ETN., Trial Registration: www.clinicaltrials.gov, NCT00844142., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In spondyloarthritis (SpA), spontaneous remission is best described in reactive arthritis, a form of peripheral SpA. Prior SpA observational studies suggested that a significant percentage of patients reached spontaneous remission; however, these patients were followed up under older, broader European Spondyloarthropathy Study Group (ESSG) criteria or were not defined by specific criteria. In general, they were mixed populations of peripheral and axial disease, and the subsets were not differentiated when assessing end points such as remission. There are limited data on the natural history of axial SpA, in part because of the evolution of the criteria with the more recently developed Assessment of SpondyloArthritis International Society (ASAS) criteria, including the designation of non-radiographic axial SpA and peripheral SpA. Clinical trials have been conducted with various remission end points including withdrawal of therapy to determine remission maintenance. The following review addresses the potential for remission in axial and peripheral SpA based on the data from both observational studies and clinical trials., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: In patients with early active axial spondyloarthritis (axSpA) with a disease duration of < 5 years, the longterm efficacy of 3 years of continuous etanercept (ETN) treatment was assessed., Methods: In a previously reported ESTHER trial, patients with axSpA were randomized to treatment with ETN (n = 40) versus sulfasalazine (SSZ; n = 36) in the first year. We analyzed the clinical, laboratory, and magnetic resonance imaging (MRI) response in the pooled dataset of patients (study population; n = 61), including patients with ankylosing spondylitis (AS, n = 31) and nonradiographic axSpA (nr-axSpA, n = 30) who were continuously treated with ETN for 3 consecutive years. Data were analyzed using the last observation carried forward and completer analysis., Results: In the entire group of patients in the study population (n = 61), the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.7 (± 1.3) at baseline to 2.6 (± 2.4) at Year 3. The Ankylosing Spondylitis Disease Activity Score (ASDAS) decreased from 3.4 (± 0.8) to 1.5 (± 1.0). Also, mean values for MRI spine and sacroiliac joint scores showed a significant decrease. Response rates in the nr-axSpA group were similar and at least as good compared to the AS group for all outcome measures. When comparing remission stages, we found that ASDAS inactive disease correlated better with C-reactive protein and MRI remission than with Assessment of SpondyloArthritis international Society partial remission., Conclusion: There was a consistent and sustained clinical response in patients with early axSpA treated with ETN over 3 years. ClinicalTrials.gov registration number NCT00844142.

Objective: We assessed whether there is a difference to etanercept (ETA) treatment in patients with ankylosing spondylitis (AS) compared with non-radiographic axial SpA (nr-axSpA) patients with a disease duration <5 years., Method: AS (n=20) and nr-axSpA (n=20) patients who were treated with ETA for 1 year were compared for differences in baseline data and treatment effect. Clinical, laboratory and MRI of sacroiliac joints (SI-joints) and spine were analysed., Results: At baseline, there were no significant differences between the 20 AS and the 20 nr-axSpA patients regarding age, disease duration, gender, HLA-B27 and clinical disease activity in terms of Bath AS Disease Activity Index (BASDAI), C-reactive protein and MRI SI-joint and spine scores in the AS compared with the nr-axSpA group. After 1 year of treatment with ETA the treatment effect was similarly good in AS and nr-axSpA (reduction of BASDAI by 3.3 (95% CI 2.2 to 3.8) vs 3.6 (95% CI 2.8 to 4.4) and reduction of AS Disease Activity Score by 1.8 (95% CI 1.5 to 2.2) vs 1.8 (95% CI 1.5 to 2.1), respectively., Conclusions: The response rate to TNF-blockers does not differ between AS and nr-axSpA if the baseline data regarding symptom duration and disease activity are similar for the two groups.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered a first-line therapy in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis. NSAIDs reduce pain and stiffness effectively in most patients, are able to reduce systemic and local inflammation, and can inhibit progression of structural damage in the spine. However, effective control of symptoms and retardation of radiographic progression often require continuous and long-term treatment, which raises safety concerns. This article discusses controversies related to the current role of NSAIDs in axSpA treatment, risks and benefits of this treatment, and current trends for individualized treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The aims of this study were (1) to assess the frequency and duration of drug-free remission and efficacy of etanercept (ETA) treatment after flare in patients with early active axial spondyloarthritis who were treated with ETA (n=40) versus sulfasalazine (SSZ, n=36) for 48 weeks and (2) to analyse the efficacy of ETA treatment in patients in year 2 who did not reach remission at week 48., Method: At week 48, patients who reached study remission (Assessment of Spondyloarthritis international Society (ASAS) plus MRI remission) were followed up without active treatment up to 1 year. In case of a flare, patients were treated with ETA for another year. All patients who were not in ASAS plus MRI remission at week 48 were treated with ETA in year 2., Results: ASAS plus MRI remission at week 48 was reached significantly more often in ETA-treated compared to SSZ-treated patients (33% vs 11%, p=0.03). However, the flare rate was not different between these two groups: 69% in the ETA group versus 75% in the SSZ group. Only 8% of patients initially treated with ETA versus 3% of those initially treated with SSZ reached permanent drug-free remission (not significant). After treatment with ETA over 1 year, patients with flare showed an improvement in all clinical and imaging variables., Conclusion: Patients with axial spondyloarthritis treated with ETA over 1 year did not reach drug-free remission in a higher percentage compared to patients from a control group treated with SSZ.

Aim: To investigate the relationship between active inflammatory lesions on whole-body MRI (wb-MRI) and new development of chronic lesions on T1 MRI in patients with early axial spondyloarthritis (SpA) treated either with etanercept (ETA) or sulfasalazine (SSZ)., Methods: Wb-MRIs of 65 patients treated either with ETA (n=35) or SSZ (n=30) over 1 year were scored for active inflammation, fatty lesions, erosions and ankylosis in the 23 vertebral units (VUs) of the spine and in the sacroiliac joints (SI joints). Scoring was performed by two blinded radiologists., Results: If there was no previous inflammation in the bone no new fatty lesions occurred in SI joint quadrants and only a few (0.6%) in spine VUs. There was a significant relationship between disappearance of inflammation and the appearance of fatty lesions: if baseline inflammation resolved fatty lesions occurred in 10.5% of SI joint quadrants and 17.9% of VUs. If inflammation did not resolve over 1 year, fatty lesions occurred less frequently: 2.4% (SI joint quadrants) and 7.2% (VUs). There was a significantly higher increase of the mean fatty lesion score between baseline and week 48 in the ETA (4.0 vs 4.8 for the SI joints and 1.9 vs 2.7 for the spine) compared to the SSZ (3.0 vs 3.2 for the SI joints and 1.1 vs 1.2 for the spine, respectively) group (p=0.001 and p=0.020 for the differences). No significant changes in the erosion or ankylosis score were observed in any of the two groups during this time., Conclusions: These data indicate that there is a close interaction between inflammation, tumour necrosis factor blockade and the development of fatty lesions in subchondral bone marrow of patients with axial SpA.

Purpose of Review: Despite overall good efficacy of currently available treatment [nonsteroidal anti-inflammatory drugs, tumor necrosis factor (TNF) α inhibitors] for ankylosing spondylitis (AS) and other spondyloarthritides (SpAs), up to 40% of the treated patients do not achieve an acceptable clinical improvement during the therapy. Here we discuss the most attractive new targets, which might become an alternative for AS/SpA patients in whom anti-TNFα therapy has failed or is contraindicated., Recent Findings: Although B-cell depletion showed a moderate efficacy in a pilot trial in anti-TNF-naïve patients with AS, inhibition of T-cell costimulation seems to be ineffective in AS but might be effective in psoriatic arthritis (PsA). Interleukin (IL)-17 blockade showed promising results in a small clinical trial in AS, anti-IL-12/23 drugs demonstrated good efficacy in PsA. Clinical trials investigating the efficacy of IL-17 blockade in PsA, as well as studies with IL-6 and IL-12/23 antagonists in AS, are currently ongoing., Summary: IL-6, IL-17, IL-12/23 and, to a latter extend, B-cells are the most promising new targets in the treatment of AS and other SpAs.

Non-steroidal anti-inflammatory drugs (NSAIDs) play different roles in the management of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). In RA there is minimal evidence that NSAIDs are able to alter the course of disease or prevent joint destruction and, therefore, they should mostly be used as a short-term bridging therapy. In contrast to RA, in AS NSAIDs are considered as a cornerstone of the treatment not only because of a high symptomatic efficacy, but also because they might even retard osteoproliferation and radiographic progression. Considering younger age of AS patients and lower prevalence of comorbidities, they are probably at lower risk for cardiovascular and gastrointestinal side effects of short- and long-term NSAID therapy in comparison to RA.