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Background: Psoriatic arthritis (PsA) is a chronic inflammatory condition predominantly affecting the peripheral joints. However, some patients with PsA can experience axial involvement which is manifested with back pain and associated with increased burden of illness., Objectives: The aim of this post hoc analysis was to determine the efficacy of ixekizumab (IXE) up to 52 weeks in reducing axial symptoms in PsA patients, presenting with axial manifestations., Design: This was a post hoc analysis of two pooled phase III clinical trials., Methods: Patients with axial manifestations, from two placebo-controlled, randomized, double-blind, phase III trials (SPIRIT-P1 and SPIRIT-P2), were defined as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 (Q2; back pain)] total score ⩾4 and average of BASDAI Q5 + Q6 (morning stiffness) ⩾4 at baseline. For this post hoc analysis, the efficacy of IXE was evaluated at weeks 16, 24, and 52 using separate BASDAI questions (including back pain and morning stiffness), total BASDAI and modified BASDAI (mBASDAI; without Q3), Ankylosing Spondylitis Disease Activity Score (ASDAS), and 50% improvement in BASDAI (BASDAI50) response. Treatment comparisons were performed using logistic regression and analysis of covariance model for categorical and continuous end points, respectively., Results: In the post hoc analysis among PsA patients with axial manifestations at baseline ( N  = 313), improvements in back pain and morning stiffness at weeks 16 and 24 were significantly greater in patients receiving IXE versus placebo (both p  < 0.001). Improvements in BASDAI individual scores and total scores, mBASDAI, and ASDAS were significantly greater in patients receiving IXE compared with placebo. Similarly, significantly more IXE-treated patients achieved BASDAI50 at weeks 16 and 24 versus placebo. The effect of IXE was sustained at week 52. Similar effects were observed in sensitivity analyses subgroups., Conclusion: IXE is effective in improving axial symptoms in patients with active PsA presenting with axial manifestations., Competing Interests: AD reports consulting fees from and has participated on advisory boards from AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Moonlake, Novartis, Pfizer, and UCB, and has received research grant from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galvani, Janssen, Novartis, Pfizer and UCB. DG reports grants or contracts from Abbvie, Amgen, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB, consulting fees from Abbvie, Amgen, BMS, Galapagos, Gilead, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB, and serves on the steering or executive committees for GRAPPA and SPARCC. PN reports consulting fees for and honoraria for lectures on behalf of Eli Lilly and Company, DP reports grants or contracts from AbbVie, Eli Lilly and Company, MSD, Novartis, and Pfizer, consulting fees from AbbVie, Biocad, Eli Lilly and Company, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis, and UCB, speaking fees from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB, RB, DMS, SYP, and SLL are employees and shareholders of Eli Lilly and Company. The Editor-in-Chief of Therapeutic Advances in Musculoskeletal Disease is an author of this paper, therefore, the peer review process was managed by alternative members of the Board and the submitting Editor was not involved in the decision-making process., (© The Author(s), 2023.)

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease which primarily affects the axial skeleton resulting in chronic back pain and stiffness. According to the guideline, the first-line treatment includes non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and non-pharmacological treatment. Second line treatment involves biological disease-modifying antirheumatic drugs (bDMARDs) such as tumour necrosis factor and interleukin-17 inhibitors., Objectives: The aim of this social media listening research project was to analyse switches of medication and the reasons thereof to gain valuable insights into real-life journeys of patients suffering from axSpA., Methods: Publicly available posts in German-speaking disease-specific forums were scanned for disease-specific keywords and commonly used drugs by axSpA patients on the Permea platform. Posts containing at least two key words were selected and switches between medications were manually labelled. A total of 287 scraped posts between 01 July 2010 and 04 Feb 2022 were analysed., Results: The largest group of described medication switches was initially using bDMARDs. Switches to a different bDMARD, termination of medication and switches to glucocorticoids were most frequently named. Patients on NSAIDs switched to glucocorticoids, a different NSAID or bDMARD, whereas patients on csDMARDs most frequently changed to bDMARDs. In all medication groups the main reason for switching was insufficient efficacy and side effects. Additionally, for the medication groups bDMARDs, csDMARDs and corticosteroids, pregnancy and lactation were given as a reason for switching, whereas patients in the NSAID group never mentioned pregnancy and breastfeeding as a reason for switching treatment., Conclusion: Our analysis shows medication switches based on real-life patient experiences shared with peers in a social listening setting. We also show medication switches differing from advised guidelines. Gathering real-life insights into patients' journey dealing with chronic diseases allows us to understand, and thereby improve patient care and treatment., (© The Author(s), 2023.)

Background: Tofacitinib is a Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA) and has been investigated for psoriasis (PsO)., Objectives: This post hoc analysis examined baseline cardiovascular (CV) disease risk and its association with the occurrence of major adverse cardiovascular events (MACE) and malignancies in tofacitinib-treated patients with PsA and PsO., Design: Included three phase III/long-term extension (LTE) PsA trials and seven phase II/phase III/LTE PsO trials of patients receiving ⩾ 1 dose of tofacitinib., Methods: Incidence rates (IRs: patients with events/100 patient-years) for MACE and malignancies (excluding non-melanoma skin cancer) were determined in subgroups according to history of atherosclerotic CV disease (ASCVD), baseline 10-year risk of ASCVD (in patients without history of ASCVD), and baseline metabolic syndrome (MetS)., Results: For patients with PsA ( N  = 783) and PsO ( N  = 3663), respectively, tofacitinib exposure was 2038 and 8950 patient-years (median duration: 3.0 and 2.4 years), and 40.9% and 32.7% had MetS. Excluding missing CV risk profile data, 51/773 (6.6%) and 144/3629 (4.0%) patients had history of ASCVD, and in patients without history of ASCVD, around 20.0% had intermediate/high baseline 10-year ASCVD risk. For PsA and PsO, IRs of MACE were greatest in those with history of ASCVD or high baseline 10-year ASCVD risk. For PsA, five of six patients with MACE had baseline MetS. Malignancy IRs in patients with PsA were greatest in those with intermediate/high baseline 10-year ASCVD risk. Of these, eight of nine patients with malignancies had baseline MetS. In the PsO cohort, IR of malignancies was notably greater with high versus low/borderline/intermediate baseline 10-year ASCVD risk., Conclusion: In tofacitinib-treated patients with PsA/PsO, increased ASCVD risk and baseline MetS were associated with higher IRs for MACE and malignancies. Our results support assessing CV risk in patients with PsA/PsO and suggest enhanced cancer monitoring in those with increased ASCVD risk., Registration Clinicaltrialsgov: NCT01877668/NCT01882439/NCT01976364/NCT00678210/NCT01710046/NCT01241591/NCT01186744/NCT01276639/NCT01309737/NCT01163253., Plain Language Summary: People who have psoriatic arthritis or psoriasis may have more heart-related problems and cancer if they have a higher risk of cardiovascular disease: A study in people with psoriatic arthritis or psoriasis receiving tofacitinib Why was this study done? • People with psoriatic arthritis (PsA) and psoriasis (PsO) are more likely than the general population to have a disease affecting the heart and blood vessels [cardiovascular (CV) disease].• People who are more likely to have CV disease may also be more likely to have certain types of cancer.• Tofacitinib is a medicine to treat people with PsA and has been tested in people with PsO.• We wanted to know if the risk of CV disease affects the number of heart-related problems (including heart attack, stroke, or death) and cancer in people with PsA and PsO. What did the researchers do? • We used results from 10 clinical trials.• In these trials, people with PsA and PsO were taking tofacitinib 5 or 10 mg twice a day.• After the trials had ended, we measured people's risk of CV disease using a risk calculator. This risk calculator showed if they had a low, borderline, intermediate, or high risk of CV disease over the next 10 years. We also checked if they had had CV disease before treatment.• We checked if people had a group of conditions linked to CV disease: diabetes, high blood pressure, and obesity.• We counted the cases of heart-related problems and cancer in people once they started taking tofacitinib. What did the researchers find? In people with PsA and PsO taking tofacitinib:• There were more cases of heart-related problems and cancer in people who had intermediate or high risk of CV disease.• There were more cases of heart-related problems in people who had had CV disease before.• More people with diabetes, high blood pressure, and obesity had heart-related problems and cancer than people without those conditions. What do the findings mean? • It is important to measure risk and assess history of CV disease in people with PsA and PsO, including those taking tofacitinib.• We should test for cancer in people with high risk of CV disease., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.E.K. has received grant/research support from Biogen, Janssen, Novartis, and UCB, and has received speaker’s fees from AbbVie, Amgen, Biogen, BMS, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc, and UCB. B.S. has acted as a consultant for AbbVie, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, CorEvitas Psoriasis Registry, Dermavant, Eli Lilly, EPI Health, Evelo Biosciences, Immunic Therapeutics, Janssen, Leo, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ono, Pfizer Inc, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv Therapeutics; has received speaker’s fees from AbbVie, Eli Lilly, Incyte, Janssen, Regeneron, and Sanofi-Genzyme; has received grants from AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Dermira, and Novartis; is a shareholder of Connect Biopharma and Mindera Health; and has received honoraria from the Journal of Psoriasis and Psoriatic Arthritis. D.P. has acted as a consultant for AbbVie, Biocad, Gilead Sciences, GlaxoSmithKline, Eli Lilly, MSD, Novartis, Pfizer Inc, Samsung Bioepis, and UCB; has received grant/research support from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer Inc; and has received speaker’s fees from AbbVie, Bristol Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer Inc, and UCB. Y-Y.L. has acted as a consultant for AbbVie, Eli Lilly, Janssen, Novartis, and Pfizer Inc. H.J. is an employee of Syneos Health, which was a paid contractor to Pfizer in connection with the development of this manuscript. K.K., I.V., D.L.F., L.F., and A.Y. are employees and shareholders of Pfizer Inc. D.D.G. has acted as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc, and UCB, and has received grants from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB., (© The Author(s), 2023.)

Objectives: The Simplified Disease Activity Index (SDAI) is a recommended composite score for assessing the remission status in patients with rheumatoid arthritis (RA). However, determination of C-reactive protein (CRP) levels takes several hours and sometimes days and limits the use of the SDAI in the clinical setting. The aim of this study was to validate the SDAI using a quick quantitative C-reactive protein (qCRP) assay (as SDAI-Q) in RA patients., Design: This is a multicenter, prospective, cross-sectional pilot study in RA patients., Methods: Adult patients (⩾18 years) with a clinical diagnosis of RA were recruited between January 2020 and September 2020 from five rheumatologic centers located in Berlin, Germany. SDAI, SDAI-Q, Clinical Disease Activity Index (CDAI), and DAS28 scores comprising CRP, qCRP, or erythrocyte sedimentation rate (ESR) were calculated. The agreement of disease activity categories was analyzed using cross tabulations and weighted Cohen's kappa. The agreement of numerical values was analyzed with Bland-Altman plots and intraclass correlation coefficients (ICCs)., Results: Overall, 100 RA patients were included in the statistical analysis. The mean value of qCRP (7.89 ± 16.98 mg/l) was slightly higher than that of routine laboratory CRP (6.97 ± 15.02 mg/l). Comparing SDAI and SDAI-Q, all patients were assigned to identical disease activity categories. Agreement of disease activity categories by CDAI and SDAI/SDAI-Q was observed in 93% with a weighted Cohen's kappa of 0.929 (95% confidence interval (CI) = 0.878; 0.981)., Conclusion: The SDAI-Q showed an absolute agreement regarding the assignment of disease activity categories in comparison with the conventional SDAI. Therefore, the SDAI-Q may facilitate the application of a treat-to-target concept in clinical trials and clinical routine as a quickly available disease activity score incorporating CRP as an objective parameter., (© The Author(s), 2022.)

The last two decades have seen major developments in the field of spondyloarthritis (SpA), but there are still important unmet needs to address. In the future, we envisage important advances in the diagnosis and treatment of SpA. In the diagnosis of SpA, the use of online and social media tools will increase awareness of the disease and facilitate the referral of patients to rheumatology clinics. In addition, more specific diagnostic tests will be available, especially advanced imaging methods and new biomarkers. This will allow most patients to be diagnosed at an early stage of the disease. In the treatment of SpA, an increasing number of novel treatment targets can be expected, most of which will be directed against intracellular enzymes. We hope to see more strategy trials shaping treatment pathways in SpA and accommodating principals of precision medicine. Approved treatment options will be available for both axial and peripheral SpA. We also hope to intervene not only at the inflammation level but also at the level of underlying immunological processes that might be associated with a higher probability of long-standing remission if not a cure. Finally, artificial intelligence techniques will allow for the analysis of large-scale data to answer relevant research questions for the diagnosis and management of patients with SpA., Competing Interests: Competing interests: The Associate Editor of Therapeutic Advances in Musculoskeletal Disease (DP) is an author of this paper, therefore, the peer review process was managed by alternative members of the Board and the submitting Editor was not involved in the decision-making process. The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: VNC received research support from AbbVie, Novartis and Pfizer; consulting fees from AbbVie, Eli Lilly, Moonlake, MSD, Novartis, Pfizer and UCB; speaker fees from AbbVie, Bristol Myers Squibb, Eli Lilly, MSD, Janssen, Novartis, Pfizer and UCB. JE received research support from AbbVie, Novartis and Pfizer; consulting fees from Eli Lilly, Novartis, Pfizer and UCB. DP received research support from AbbVie, Eli Lilly, MSD, Novartis, Pfizer; consulting fees from AbbVie, BIOCAD, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB; speaker fees from AbbVie, Bristol Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer and UCB., (© The Author(s), 2022.)

Objectives: The objective of the study was to validate the Ankylosing Spondylitis Disease Activity Score (ASDAS) based on a quick quantitative C-reactive protein (qCRP) assay (ASDAS-Q) in a multicentre, prospective, cross-sectional study in patients with axial spondyloarthritis (axial SpA)., Methods: Disease activity assessment was performed in prospectively recruited patients with axial SpA. Routine laboratory CRP was determined in the central laboratory of each study centre, while quick qCRP and erythrocyte sedimentation rate (ESR) were measured locally. Consequently, ASDAS-CRP, ASDAS-Q using the qCRP and ASDAS-ESR were calculated. The absolute agreement on the disease activity category ascertainment was analysed with cross-tabulations and weighted Cohen's kappa. Bland-Altman plots and intraclass correlation coefficients (ICCs) were used to analyse the criterion validity., Results: Overall, 251 axial SpA patients were included in the analysis. The mean qCRP value (6.34 ± 11.13 mg/l) was higher than that of routine laboratory CRP (5.26 ± 9.35 mg/l). The ICC for routine laboratory CRP versus qCRP was 0.985 [95% confidence interval (CI): 0.972-0.991]. Comparing ASDAS-Q with ASDAS-CRP, 242 of 251 (96.4%) patients were assigned to the same disease activity categories with a weighted Cohen's kappa of 0.966 (95% CI: 0.943-0.988) and ICC of 0.997 (95% CI: 0.994-0.999)., Conclusions: ASDAS-Q showed an almost perfect agreement with ASDAS-CRP in the assignment to specific disease activity categories. Consequently, ASDAS-Q using the qCRP value can be applied as an accurate and quickly available alternative to ASDAS-CRP, thus facilitating the implementation of the treat-to-target concept in clinical trials and clinical routine., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: FP: reports grants and personal fees from Novartis, Lilly and UCB and personal fees from AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer and Roche all outside the presented work. JBJ: reports personal fees from AbbVie, Affibody, BMS, Gilead, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis and UCB all outside the presented work. GRB: reports personal fees from AbbVie, Lilly, Janssen, Novartis, Amgen and Pfizer all outside the presented work. HH: reports personal fees from from Janssen, AbbVie, MSD, Pfizer, Novartis and Roche all outside the presented work. KK: reports personal fees from AbbVie, Lilly, Roche, Novartis, Sanofi and Galapagos all outside the presented work. BM: reports personal fees from UCB, Amgen, Gilead and Hexal Sandoz all outside the presented work. DP: reports grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis and Pfizer, and personal fees from Bristol-Myers Squibb, Roche, UCB, Biocad, GlaxoSmithKline and Gilead all outside the presented work. JS, HCB, HK, SL, MP, VRR, MT, MV and SZ have nothing to disclose., (© The Author(s), 2022.)

Background: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research., Design: Prospective, multicenter, multinational, cross-sectional study., Methods and Analyses: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information., Ethics: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DP: reports grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis and Pfizer, and personal fees from Bristol Myers Squibb, Roche, UCB, Biocad, GlaxoSmithKline and Gilead. XB: reports grants and personal fees from AbbVie and Novartis, and personal fees BMS, Chugai, Eli Lilly, MSD, Pfizer, UCB, Galapagos and Gilead. FVdB: received speaker and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB. JB: has received honoraria for talks, advisory boards, paid consultancies and grants for studies from Abbvie (Abbott), Amgen, Baxter, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Fresenius, GlaxoSmithKline, Gilead, Hexal, Janssen, Lilly, Medac, MSD (Schering-Plough), Mylan, Mundipharma, Novartis, Pfizer (Wyeth, Hospira), Roche, Sanofi-Aventis and UCB. LCC: reports grant/research support from Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer and honoraria from Abbvie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Galapagos, Gilead, GSK, Janssen, Lilly, Medac, Novartis, Pfizer and UCB. VC: reports honoraria and/or research grants from Abbvie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and is supported by a Pfizer Chair Rheumatology Research Award from the Department of Medicine, University of Toronto; spouse is an employee of AstraZeneca. TD: reports personal fees from Novartis Pharma, MSD and Canon MS, outside the submitted work. FAvG: reports grants from Stichting vrienden van Sole Mio, Stichting ASAS, UCB and Novartis and honoraria from Novartis, MSD, Abb Vie and Bristol Myers Squibb. LSG: reports grants and personal fees from UCB and Pfizer, and personal fees from AbbVie, Eli Lilly, Janssen and Novartis. NG: Employed by Abcuro, Inc; stockholder UCB. ABG: received honoraria as an advisory board member and consultant for AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb Co., Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB, Dermavant and Xbiotech. ABG has received research / educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB, Xbiotech and Sun Pharma. DvdH: reports personal fees from 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 and UCB Pharma, outside the submitted work; and Director of Imaging Rheumatology bv. PSH: received consulting fees (Eli Lilly) and fees for educational services (Pfizer, Novartis, Janssen). KGAH: reports lecture fees from AbbVie, MSD, Pfizer and Novartis. DJ: Although not directly related to this manuscript, DJ has received research grants, educational grants and/or speaker honoraria from AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Eli Lilly, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. DJ acknowledges that his research time is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-42001) and Cambridge Arthritis Research Endeavour (CARE). RGL: has acted as a paid consultant for Calyx, CARE Arthritis, IA Group, Novartis and Pfizer. WPM: is Chief Medical Officer of CARE Arthritis Ltd and has acted as a paid consultant/participated in advisory boards for AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB; received research and/or educational grants from AbbVie, Novartis, Pfizer and UCB; and received speaker fees from AbbVie, Janssen, Novartis, Pfizer and UCB. PM: reports grants and personal fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun and UCB, and personal fees from Boehringer Ingelheim and GlaxoSmithKline. PN: reports consulting / speaker fees from Abbvie, Bristol Myers Squibb, Gilead, Janssen, Novartis, Lilly, Pfizer, Celgene, Roche, Boehringer, Sanofi, Merck, outside the submitted work. FP: reports grants and personal fees from Novartis, Lilly and UCB, and personal fees from AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer and Roche. MP: reports personal fees from Novartis. DDG: Grant support from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UBC, and consulting fees from Abbvie, Amgen, BMS, Galapagos, Gilead, Eli Lilly, Janssen, Novartis, Pfizer and UCB. JS: has nothing to disclose. MT: has nothing to disclose., (© The Author(s), 2021.)

Background: This study aimed to evaluate the efficacy and safety of secukinumab 150 mg compared with placebo in the management of spinal pain and disease activity in patients with axial spondyloarthritis (axSpA) at Week 8 and up to Week 24., Methods: Patients ( n  = 380) with active axSpA were randomized (3:1) to secukinumab 150 mg (Group A) or placebo (Group B). At Week 8, patients from Group A with an average spinal pain score <4 were defined as responders and were re-assigned to secukinumab 150 mg (Arm A1); whereas non-responders were re-randomized to secukinumab 150/300 mg (Arm A2/A3). Patients from Group B were re-randomized (1:1) to secukinumab 150/300 mg (Arm B1/B2)., Results: At Week 8, the odds of achieving an average spinal pain score of <4 were significantly higher for patients on secukinumab 150 mg than for patients on placebo (odds ratio (OR): 1.89; 95% confidence interval (CI): 1.08-3.33; p  = 0.0264). Further reductions in spinal pain were observed across treatment groups up to Week 24. Pronounced improvements were also observed in other disease activity measurements, such as Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Disease Activity Score. Responders from Group A showed the highest improvements for all measured parameters of spinal pain compared with the other arms. No new or unexpected safety signals were observed., Conclusion: Secukinumab provided rapid and significant improvement in spinal pain at Week 8 which was sustained or increased further up to Week 24 in patients with axSpA., Trial Registration: ClinicalTrials.gov: NCT03136861. Registered May 2, 2017., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DP received grant/research support from AbbVie, MSD, Novartis, and Pfizer, and a consultant/speaker for AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, and UCB. EP is an employee of Novartis and owns Novartis Stock. AZ is a consultant for Novartis and Pfizer. AB is a consultant for AbbVie and on the speaker’s bureau of Novartis, AbbVie, Amgen, Roche, and KRKA. SS and BS are employees of Novartis. MR and CP are employees of Novartis and own Novartis Stock. HM-O received grant/research support from Janssen and Novartis, a consultant for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, and on the speaker’s bureau of AbbVie, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Takeda, and UCB. The remaining author had no conflicts to declare., (© The Author(s), 2021.)

Aims: Long-term data on TNFi treatment in patients with axSpA is scarce. The objective of this analysis was to assess long-term clinical efficacy of etanercept in early axSpA [including both non-radiographic and radiographic axSpA forms], who participated in the long-term (until year 10) extension of the ESTHER-trial., Methods: In the previously reported ESTHER-trial, patients with early active axSpA were randomized to treatment with etanercept ( n  = 40) or sulfasalazine ( n  = 36) during the first year. Patients in remission discontinued their therapy and were followed up until the end of year 2; in case of remission-loss, etanercept was (re)-introduced and continued until the end of year 10. If remission was not achieved at year 1, patients continued receiving (or were switched to) etanercept for up to 10 years., Results: A total of 19 patients (12 with r-axSpA and 7 with nr-axSpA at baseline) out of the initial 76 patients (= 25%) completed year 10 of the study. In the entire group, a sustained clinical response was seen over 10 years of follow up in the as-observed analysis. Completers were significantly more often male and showed lower values of patient and physician global assessments of disease activity, Ankylosing Spondylitis Disease Activity Score (ASDAS), and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) scores at baseline as compared with non-completers. When analyzing clinical data of the completers, mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values were constantly below 2 and mean ASDAS below 2.1 during follow up with no statistically significant differences between the r-axSpA and nr-axSpA subgroups. A total of 39 serious adverse events were documented over the 10 years, while six of them were seen as possibly associated with the etanercept treatment, which led in five patients to treatment discontinuation., Conclusion: A sustained clinical response was observed over the 10 years of the study with comparable response and drop-out rates between r-axSpA and nr-axSpA. Etanercept was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals., Competing Interests: Conflict of interest statement: FP: research grants from Novartis; speaker and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, and UCB Pharma. AW: has nothing to disclose. MT: has nothing to disclose. MP: speaker and consulting fees from AbbVie and Novartis. VRR: speaker and consulting fees from AbbVie and Novartis. HH: speaker and consulting fees from Janssen, MSD, Novartis, Pfizer, and Roche. OB: employee of Pfizer. JS: research grants from AbbVie, Janssen, MSD, Pfizer, Roche; speaker and consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB Pharma. DP: research grants from AbbVie, MSD, Novartis, and Pfizer; speaker and/or consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Gilead, Eli Lilly and Company, GlaxoSmithKline, MSD, Novartis, Pfizer, Roche, and UCB Pharma., (© The Author(s), 2021.)

Spondyloarthritides (SpA) like psoriatic arthritis, axial spondyloarthritis/ankylosing spondylitis, reactive arthritis and inflammatory bowel disease (IBD)-associated SpA can present with characteristic skin manifestations. These SpA-associated skin disorders may precede joint involvement, reflect a loss of efficacy of a current systemic treatment or can even be treatment associated. Cutaneous manifestations in SpA not only add additional morbidity with physical impact but also impose a psychosocial burden on affected patients. Psoriasis (PsO) - the main skin disease in SpA - has a variety of clinical presentations, including plaque-type PsO, inverse PsO, guttate PsO, erythrodermic PsO, nail PsO and pustular types. SpA associated with IBD presents with neutrophilic and granulomatous skin disorders, including pyoderma gangrenosum, hidradenitis suppurativa and cutaneous Crohn's disease. Reactive arthritides has a favourable prognosis and may feature keratoderma blenorrhagicum or balanitis circinatum as typical skin manifestations. Immunologically, SpA-associated skin diseases share interleukin (IL)-17 and IL-23 dysregulation but show distinctive genetic and immunological profiles. Therefore, they vary in their treatment responses to targeted therapies with biologicals or small molecules. In this review, we highlight the clinical presentation of skin manifestations in SpA and discuss therapeutic approaches in this interdisciplinary field., Competing Interests: Conflict of interest statement: KM has received honoraria or travel expenses for lecture and research activities from Abbvie, Biogen, Celgene, Janssen-Cilag and UCB Pharma. AS has received travel expenses from Janssen-Cilag and Celgene DP has received grant/research support from AbbVie, Lilly, MSD, Novartis, and Pfizer; has been a consultant for AbbVie, Biocad, Gilead, GSK, Lilly, MSD, Novartis, Pfizer, Samsung and UCB; and served on the speakers bureau for AbbVie, BMS, Lilly, MSD, Novartis, Pfizer and UCB. KG has received honoraria or travel expenses for lecture and research activities from Abbvie, Almirall, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Delenex, Eli Lilly, Galderma, Janssen-Cilag, Medac, MSD, Novartis, Pfizer and UCB Pharma., (© The Author(s), 2020.)

Objective: The aim of this study was to investigate the association of extra-musculoskeletal manifestations (EMMs) with disease activity, functional status, and treatment patterns in a large population-based cohort of patients with axial spondyloarthritis (axSpA)., Methods: A stratified random sample of patients with axSpA, drawn from health insurance data, received a survey on disease-related characteristics including history (ever presence) of the following EMMs: inflammatory bowel disease (IBD), psoriasis (PSO), and anterior uveitis (AU). Survey data were linked to health insurance data, gathering additional information on current occurrence (within one year) of EMMs and drug prescriptions. Separate multivariable linear regression models were calculated to determine the association of EMMs with disease activity (Bath Ankylosing Spondylitis Disease Activity Index), and functional status (Bath Ankylosing Spondylitis Functional Index) after adjustment for relevant parameters, including treatment., Results: A total of 1729 patients with axSpA were included in the analyses (response: 47%; mean age: 56 years; 46% female) of whom 6% (9%) had current (ever) IBD, 10% (15%) had current (ever) PSO, and 9% (27%) had current (ever) AU. Ever presence of IBD and history of PSO were significantly associated with higher level of disease activity. Ever presence of PSO was also associated with higher level of functional impairment, whereas current AU was significantly associated with lower disease activity. Patients with current IBD or PSO received more frequently biological and conventional synthetic disease-modifying anti-rheumatic drugs as well as systemic steroids. AU was associated with a higher use of conventional synthetic disease-modifying anti-rheumatic drugs only., Conclusion: Disease activity is higher in patients with axSpA with history of IBD or history of PSO. Functional impairment is also higher in patients with axSpA with history of PSO. The presence of different EMMs was associated with different treatment patterns in axSpA., Competing Interests: Conflict of interest statement: I. Redeker, J. Callhoff, F. Hoffmann, A. Zink declare no conflicts of interest. U. Marschall is an employee of BARMER. H. Haibel reports consulting fees or members of speakers’ bureau from AbbVie, Janssen, MSD, Novartis, Pfizer, and Roche. B. Siegmund, has served as a consultant for AbbVie, Boehringer, Celgene, Falk, Janssen, Lilly, Pfizer, Prometheus, Takeda and received speaker’s fees from AbbVie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, Takeda (BS served as representative of the Charité). J. Sieper reports consulting fees or members of speakers’ bureau from AbbVie, Janssen, Lilly, MSD, Novartis, and Pfizer and grants from AbbVie, MSD, and Pfizer. D. Poddubnyy reports consulting fees or members of speaker’s bureau from AbbVie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, and UCB and grants from AbbVie, MSD, Novartis and Pfizer., (© The Author(s), 2020.)

Uveitis is the most frequent extra-articular manifestation of axial spondyloarthritis (SpA), occurring in up to one-third of the patients. In the majority of patients, uveitis is acute, anterior and unilateral and presents with photosensitivity, sudden onset of pain and blurred vision. Topical steroids are an effective treatment; however, recurrent or refractory cases may need conventional disease-modifying antirheumatic drugs or biological treatment with monoclonal tumor necrosis factor (TNF) inhibitors, thus also influencing treatment strategy of the underlying SpA. Though the exact pathogenesis of SpA and uveitis remains unknown, both seem to result from the interaction of a specific, mostly shared genetical background (among other HLA-B27 positivity), external influences such as microbiome, bacterial infection or mechanical stress and activation of the immune system resulting in inflammation. Up to 40% of patients presenting with acute anterior uveitis (AAU) have an undiagnosed SpA. Therefore, an effective referral strategy for AAU patients is needed to shorten the diagnostic delay of SpA and enable an early effective treatment. Further, the risk for ophthalmological manifestations increases with the disease duration in SpA; and patients presenting with ocular symptoms should be referred to an ophthalmologist. Thus, a close collaboration between patient, rheumatologist and ophthalmologist is needed to optimally manage ocular inflammation in SpA., Competing Interests: Conflict of interest statement: JR: grant/research support from AbbVie, consultancy for Novartis. DP research grants from: AbbVie, Lilly, MSD, Novartis, Pfizer. Consultancy/speaker fees from: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. UP served as principal investigator or consultant for: Abbvie, Alcon, Allergan, Alimera, Bayer, Dompé, Lilly, Novartis, Santen, Shire, Thea and Winzer., (© The Author(s), 2020.)

Biologics are substances synthetized from biological sources used in the prevention and treatment of several diseases. Rheumatologists have many years of experience with biologics for the treatment of immune-mediated diseases and osteoporosis. Randomized clinical trials and postmarketing studies have demonstrated that treatment with biologics can result, albeit infrequently, in serious adverse events. To date, several risk mitigation strategies have been identified and implemented. The objective of the present perspective review is to examine the risk mitigation strategies of biologic treatments, with special focus on anti-tumor necrosis factors and denosumab., Competing Interests: Conflict of interest statement: Giovanni Adami declares that he has no conflict of interest. Kenneth G. Saag declares a research grant from Amgen and Merck and a consultant fee from Amgen, Lilly, Merck and Radius and Roche. Roland D. Chapurlat declares a research grant from Amgen, Merck, Chugai, UCB and a speaker/consultant fee from Amgen, Lilly, UCB, BMS, Abbvie, Pfizer, Arrow, Ultragenyx and Chugai. Nuria Guañabens declares a speaker/consultant fee from Alexion, Amgen, Eli Lilly and UCB. Glenn Haugeberg declares a research grant, speaker fees, and/or consultant fees from Amgen Pfizer, UCB, Abbott, Lilly, Novartis, Roche, and Biogen. Willem F. Lems declares a speaker/consultant fee from Pfizer, Amgen, Eli Lilly and UCB. Matijevic Radmila declares that she has no conflict of interest. Nicola Peel declares that she has no conflict of interest. Denis Poddubnyy declares a research grant from Abbvie, Merck, Novartis, Pfizer and a speaker/consultant fee from Abbvie, BMS, Boehringer, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. Piet Geusens declares a research grant from Amgen, Pfizer, Merck, UCB, Abbott, Lilly, BMS, Novartis, Roche, Will Pharma and a speaker/consultant fee from Amgen and Lilly., (© The Author(s), 2019.)

Development of the Assessment in Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (SpA) was one of the major breakthroughs in the field over the past decade. Despite some concerns related to the specificity of the criteria, they stimulated research into the early stage of the disease. This resulted in major advances in the understanding of the course of the disease, revealing predictors of progression, improvement in early diagnosis and treatment in axial SpA. In this review, we summarize the recent developments resulting from the introduction of the ASAS classification criteria for axial SpA and the implications for research and clinical practice., Competing Interests: Conflict of interest statement: The authors declare no conflict of interests in preparing this article.

Nonradiographic axial spondyloarthritis (SpA) and radiographic SpA (also known as ankylosing spondylitis) are currently considered as two stages or forms of one disease (axial SpA). The treatment with tumor necrosis factor-α (TNFα) inhibitors has been authorized for years for ankylosing spondylitis. In recent years, most of the anti-TNFα agents have also been approved for the treatment of nonradiographic axial SpA by the European Medicines Agency (EMA) and similar authorities in many countries around the world (but not in the US), increasing the number of possible therapies for this indication. Data from several clinical trials have demonstrated the good efficacy and safety profiles from those anti-TNFα agents. Presently, a large number of patients achieve a satisfactory clinical control with the current therapies, however, there remains a percentage refractory to nonsteroidal anti-inflammatory drugs (NSAIDs) and TNFα inhibitors; therefore, several new drugs are currently under investigation. In 2015, the first representative of a new class of biologics [an interleukin (IL)-17 inhibitor] secukinumab, was approved for the treatment of ankylosing spondylitis; a clinical trial in nonradiographic axial SpA is currently underway. In this review, we discuss the recent data on efficacy and safety of TNFα-inhibitors focusing on the treatment of nonradiographic axial SpA., Competing Interests: Conflict of interest statement: VR: none declared; DP: received grant/research support from AbbVie, MSD, Novartis, Pfizer; consultant for: AbbVie, BMS, Boehringer, MSD, Novartis, Pfizer, and UCB; speakers bureau: AbbVie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). Nonradiographic axSpA (axSpA without radiographic sacroiliitis) and ankylosing spondylitis (AS; radiographic form of axSpA) are considered nowadays as two consecutive stages of one disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective against the major symptoms of axSpA (pain and stiffness) and may have disease-modifying properties including retarding progression of structural damage in the spine. Therefore, NSAIDs, unless contraindicated, are the treatment of choice for the majority of patients with axSpA. Beyond NSAIDs, only tumour necrosis factor (TNF) α blockers are effective and approved for the treatment of active axSpA. Several novel drugs (i.e. monoclonal antibodies targeting interleukin-17, interleukin-12/23, inhibitors of phosphodiesterase-4 and kinases), which might be effective in axSpA, are currently under investigation. Pharmacological therapy of axSpA should always be combined with nonpharmacological treatment including education and regular exercise/physiotherapy.