Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial.

OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.

Generalized pustular psoriasis-like widespread eruption following COVID-19 infection in a patient with spondyloarthropathy on adalimumab.

Generalized pustular psoriasis (GPP) is a form of pustular psoriasis that is distinguished by recurring or persistent outbreaks of non-acral primary sterile pustules. These eruptions can occur with or without systemic inflammation. Various factors, such as medications, stress and viral infection, have been identified as potential triggers for GPP flares. While several cases have detailed GPP-like eruptions in the setting of coronavirus disease 2019 (COVID-19) infection, few have explored the interplay between infection and biologic use in the development of GPP. In this case, we detail the history and management of a 45-year-old male patient with a prior history of spondyloarthropathy managed on a tumour necrosis factor-α inhibitor and recent COVID-19 infection presenting with a new, spreading pustular rash.

Clinical efficacy of JAK inhibitors on enthesitis in spondyloarthropathy: A scoping literature review.

BACKGROUND: Enthesitis is a key feature of spondyloarthropathy (SpA). In recent years, JAK inhibitors have emerged as efficacious drugs in the landscape of advanced therapies for patients with SpA. METHOD: The aim of this scoping literature review was to search the published literature for studies on JAK inhibitors and their effects on enthesitis in patients with SpA and evaluate the data and summarise the findings. The clinical trials reviewed used the Leeds Enthesitis Index, Spondyloarthritis Research Consortium of Canada Enthesitis Index, and Maastrich Ankylosing Spondylitis Enthesitis Score as outcome measures. RESULTS: Tofacitinib, upadacitinib, and filgotinib had numerically greater reductions in the enthesitis scores when compared with placebo. CONCLUSION: While the JAK inhibitors are therapeutic options for enthesitis in SpA, head-to-head studies are needed to compare the JAK inhibitors against the biological drugs (targeting TNF, IL-17, and IL-12/23) as well as studies showing the effects of JAK inhibitors on enthesitis imaging.

When to start secukinumab treatment in patients with axial spondyloarthropathy: Before or after anti-TNFα treatment?

INTRODUCTION AND OBJECTIVES: This study aimed to evaluate the efficacy of secukinumab (SEC) in axial spondyloarthropathy (axSpA) in anti-TNFα naïve and anti-TNFα experienced patients. It also focused on the duration of SEC treatment and its side effects. PATIENTS AND METHODS: The patients with axSpA treated with SEC and followed up in our outpatient clinic from May 2018 through October 2021 were included in this study. All patients in the study also fulfilled the ASAS classification criteria for axSpA. Patients were separated into two groups according to whether they received prior anti-TNFα therapy. While anti-TNFα naïve patients comprised group 1, anti-TNFα experienced patients were included in group 2. Pre- and post-treatment BASDAI scores were reported and compared. RESULTS: Eighty-four axSpA patients (42 men; duration of the disease: 86.86±65.35 months in group 1 and 160.65±97.4 months in group 2) were treated with SEC. 45.5% of anti-TNFα naïve patients and 56.5% of anti-TNFα experienced patients were still on SEC therapy in October 2021. Duration of SEC treatment was 12.5±7.9 months in group 1 and 17.19±12 months in group 2 (p=0.098). The differences between pre-and post-treatment BASDAI scores were statistically significant in both groups (p<0.001). While patients in group 1 did not develop any adverse effects, three patients in group 2 experienced alopecia, uveitis, and recurrent pneumonia after SEC treatment. CONCLUSION: Our study's efficacy and safety data on the use of SEC were reassuring in both anti-TNFα naïve and anti-TNFα experienced patients. However, further studies are still needed to determine the appropriate timing to begin SEC treatment.

Seronegative spondyloarthropathy-associated inflammatory bowel disease.

Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.

Clinical Features and Outcomes of Coronavirus Disease 2019 in Patients with Inflammatory Bowel Disease and Spondyloarthropathies.

BACKGROUND: We aimed to determine the clinical features, predictive factors associated with severe disease, and outcomes of coronavirus disease 2019 in patients with immune-mediated inflammatory diseases and report data on the comparison of coronavirus disease 2019 between patients with inflammatory bowel disease and spondyloarthropathies. METHODS: A total of 101 patients with inflammatory bowel disease and spondyloarthropathies who had confirmed diagnosis of coronavirus disease 2019 were retrospectively analyzed. Demographics, comorbidities, immunosuppressive treatments, and the impact of immunosuppression on negative outcomes were assessed. RESULTS: The median age of the patients was 47 (38-57) years. The most common rheumatologic diagnosis was ankylosing spondylitis (n = 24), psoriatic arthritis (n = 17), and reactive arthritis (n = 1). In the inflammatory bowel disease group, 47 patients had ulcerative colitis, 11 Crohn's disease, and 1 unclassified. The most commonly used treatments were biologics (55%) in the spondyloarthropathies group and aminosalicylates (66.1%) in the inflammatory bowel disease group. Overall, 18.8% of the patients required hospitalization, 5% developed severe complications, and 2% died. There were no significant differences in coronavirus disease 2019-related negative outcomes between spondyloarthropathies and inflammatory bowel disease patients. The median age was higher in the patients who required hospitalization [57 (46-66) vs 47 (38-57) years, P=.008]. Bilateral opacities on chest radiographs were more common in the patients who required hospitalization in the spondyloarthropathies group [88.9% vs 14.3%, P=.016]. Comorbidity was significantly associated with hospitalization in the inflammatory bowel disease group (P ≤ .05). Baseline therapy with biologics or immunosuppressives was not associated with severe coronavirus disease 2019 outcomes. CONCLUSION: Older age, comorbidities, and bilateral ground-glass opacities were associated with adverse outcomes, whereas specific immune-mediated inflammatory disease diagnoses or immunosuppressive treatments were not.

Spondyloarthropathy in Inflammatory Bowel Disease: From Pathophysiology to Pharmacological Targets.

Spondyloarthritis (SpA) represents one of the most frequent extraintestinal manifestations of inflammatory bowel disease (IBD). Evidence of shared genetic and molecular pathways underlying both diseases is emerging, which has led to rational approaches when treating patients with concomitant diseases. Clinical efficacy of tumor necrosis factor (TNF) antagonists has been ascertained over the years, and they currently represent the cornerstone of treatment in patients with IBD and SpA, but the therapeutic armamentarium in these cases has been recently expanded. Evidence for vedolizumab is controversial, as it was associated both with improvement and development of arthralgias, while ustekinumab, the first anti-interleukin 12/23 (IL-12/23) approved for IBD, has demonstrated good efficacy, especially in peripheral arthritis, and more IL-23 inhibitors are being developed in IBD. Tofacitinib was the first Janus kinase (JAK) inhibitor to be approved in IBD, and as it demonstrated efficacy in treating ankylosing spondylitis, it may represent a good choice in axial arthritis, while more selective JAK inhibitors are yet to be approved. Unexpectedly, the first anti-IL17 that was studied in IBD (secukinumab) has shown not to be effective in treating IBD, and the role of anti-IL17 drugs in these diseases needs further investigation. Therefore, as availability of biologics and small molecules is increasing, their positioning in clinical practice is becoming more and more challenging, and multidisciplinary management needs to be implemented in both research and clinical settings in order to enhance early recognition of SpA in IBD patients, optimize treatment and ultimately improve the patients' quality of life.

Factors associated with drug-free remission at 5-year in early onset axial spondyloarthritis patients: Data from the DESIR cohort.

OBJECTIVES: To assess the frequency of patients in drug-free remission at 5 years in a cohort of early axial SpA, and the factors associated with this remission. METHODS: Patients: patients included in the DESIR (DEvenir des Spondyloarthropathies Indifférenciées Récentes) cohort undergoing the 5-year visit were selected for this analysis. Definition of 5-year drug-free remission: (1) all patients in ASAS partial remission and/or ASDAS<1.3 at 5 year visit and (2) taking no disease modifying anti-rheumatic drugs at the 5-year visit and (3) with an ASAS-NSAID score≤25 at the 5-year visit. DATA ANALYSIS: the proportion of patients in drug-free remission was described. The association between demographic, clinical, biological and imaging characteristics and drug-free remission at 5 years was assessed by logistic regression. RESULTS: Of the 412 patients included in this analysis, 73 (18%) were in drug-free remission at the 5-year visit. The baseline clinical factors associated with the chances to be in drug-free remission at the 5-year visit were symptom duration (OR=0.66 [95%CI%: 0.44-0.97]), lower HAQ-AS score (OR=0.32 [0.12-0.78]), lower ASDAS score (OR=0.55 [95%CI: 0.34-0.86]), ASAS-NSAID score (OR=0.91 [95%CI: 0.82-0.99]). Furthermore, anti-TNF use (OR=0.20 [95%CI: 0.08-0.42]) during the follow-up decreased the chances of being in 5-year drug-free remission. CONCLUSION: The probability of being in drug free remission at 5 year when beginning an axial SpA is low and is associated with lower baseline disease activity and functional scores, while starting an anti-TNF is associated with poor chances of later being in drug-free remission. NCT01648907.

Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care: does the choice of biological therapy matter?

BACKGROUND: The effect of interleukin 17-inhibitors on anterior uveitis (AU) in spondyloarthritis (SpA) is poorly understood. This study aimed to compare the risk of AU during treatment with secukinumab versus tumour necrosis factor inhibitors (TNFi). METHODS: Patients with SpA starting secukinumab or a TNFi 2015 through 2018 were identified in the Swedish Rheumatology Quality Register. Occurrence of AU was identified based on diagnosis codes in outpatient ophthalmology care in the National Patient Register. The main outcomes were crude rates of AU-diagnoses per 100 patient-years, and adjusted HRs for AU, during treatment, in patients without AU during the year before treatment start (in order to reduce confounding by indication). HRs were adjusted for age, sex, history of AU and patient global assessment of disease activity. RESULTS: Based on 4851 treatment starts (456 secukinumab; 4395 any TNFi), the rate of AU-diagnoses per 100 patient-years was 6.8 (95% CI 5.2 to 8.7) for secukinumab. Among the TNFi, the rate varied from 2.9 (95% CI 2.1 to 3.7) for infliximab and 4.0 (95% CI 3.3 to 4.9) for adalimumab to 7.5 (95% CI 6.7 to 8.4) for etanercept. The adjusted HRs for first AU (adalimumab as reference) were: secukinumab 2.32 (95% CI 1.16 to 4.63), infliximab 0.99 (95% CI 0.49 to 1.96), etanercept 1.82 (95% CI 1.13 to 2.93), golimumab 1.59 (95% CI 0.90 to 2.80) and certolizumab 1.12 (95% CI 0.44 to 2.83). Sensitivity analyses confirmed the pattern of higher AU rates with secukinumab and etanercept versus monoclonal TNFi. CONCLUSION: As used in clinical practice in SpA, secukinumab appears to be associated with a higher risk of AU, compared with the monoclonal TNFi and a similar risk compared with etanercept.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

JAK1 selective inhibitors for the treatment of spondyloarthropathies.

As our understanding of the pathogenesis of SpA improves, focus has turned to the role janus kinase (JAK)-mediated signal transduction and inhibiting its actions as a therapeutic mechanism. Small molecule inhibitors of JAK exist, with variable selectivity for the different JAK isoforms. Less selective JAK inhibitors have variable efficacy and safety profiles, prompting the investigation of selective JAK1 inhibition. In this review, we summarize the current phase 2 and 3 clinical trial data, evaluating the use of JAK1 selective inhibitors in the treatment of SpA, particularly AS and PsA. Selective JAK1 inhibition offers a promising therapeutic approach, however further longer-term trials are needed to fully establish their efficacy and safety at higher doses, and their use in the greater continuum of SpA.

JAK1: Number one in the family; number one in inflammation?

Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine. JAK1 is involved in the signalling of 'γc' receptor cytokines (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), pro-inflammatory cytokines including IL-6, as well as IFN. The critical position of JAK1 downstream of these cytokines suggests that JAK1-selective inhibitors are comparable to non-selective ones, without the unwanted consequences of JAK2- or JAK3-blockade. JAK inhibition has led to a better understanding of the biology of synovial inflammation and bone homeostasis. Moreover, the efficacy of non-selective JAK inhibitors and novel JAK1-selective drugs in RA supports a role for JAK1 in its pathogenesis. JAK1-selective drugs are also showing promise in axial spondyloarthritis, suggesting that they may target additional regulatory pathways that impact cytokines such as TNF and IL-17A, which do not use JAKs. Additionally, evidence now supports a JAK1 predominance in the signalling of IL-6 and oncostatin M, and indirectly, of TNF in synovial fibroblasts, macrophages and endothelial cells. Notably, bone homeostasis is also dependent on cytokines relying on JAK1 signalling to promote receptor activator of NF-κB ligand expression in osteoblasts and T cells, contributing to osteoclastogenesis. Here, the contribution of JAK1 over other kinases is unclear. While beneficial effects of JAK inhibitors on bone erosion are supported by preclinical and clinical data, effects on new bone formation in axial spondyloarthritis requires additional study.

Comparative effectiveness of two adalimumab biosimilars in 1318 real-world patients with inflammatory rheumatic disease mandated to switch from originator adalimumab: nationwide observational study emulating a randomised clinical trial.

OBJECTIVES: In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondyloarthritis (AxSpA). METHODS: Observational cohort study based on the DANBIO registry with geographical cluster pseudo-randomisation, analysed by emulating a randomised clinical trial. Main outcome was adjusted 1-year treatment retention (Cox regression). Furthermore, 6 months' remission rates (logistic regression), reasons for withdrawal and back-switching to originator were investigated (overall and stratified by indication). RESULTS: Overall, of 1570 eligible patients, 1318 switched and were included (467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to SB5. Baseline characteristics of the two clusters were largely similar, but some differences in registration practice were observed. The combined 1-year retention rate for the two biosimilars was 89.5%. Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR 0.60; 95% CI 0.42 to 0.86) and 6 months' remission rate was higher (OR 1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results (statistically significant for RA). During 1 year, 8.5% and 12.9% withdrew GP2017 and SB5, respectively (primarily lack of effect and adverse events), of whom 48 patients (3.6%) back-switched. CONCLUSION: This head-to-head comparison of GP2017 versus SB5 following a mandatory switch from the originator indicated differences in effectiveness in routine care. This may reflect a true difference, but other explanations, for example, differences in excipients, differences between clusters and residual confounding cannot be ruled out.

Tumor Necrosis Factor Inhibitors Reduce Spinal Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: A Longitudinal Analysis From the Alberta Prospective Cohort.

OBJECTIVE: To investigate whether tumor necrosis factor inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (SpA) and whether this is coupled to their effect on inflammation. METHODS: Patients with axial SpA fulfilling the modified New York criteria were included in a prospective cohort (the ALBERTA Follow Up Research Cohort in Ankylosing Spondylitis Treatment). Spine radiographs, performed every 2 years for up to 10 years, were scored by 2 central readers, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS was evaluated with generalized estimating equations by testing the interaction between TNFi and Ankylosing Spondylitis Disease Activity Score (ASDAS) at the start of each 2-year interval (t). If significant, the association between ASDAS at t and mSASSS at the end of the interval (t+1) was assessed in 1) patients treated with TNFi at all visits, 2) patients treated with TNFi at some visits, and 3) patients who were never treated with TNFi. In addition, the association between TNFi at t and mSASSS at t+1 (adjusting for ASDAS at t) was also tested (direct effect). RESULTS: In total, 314 patients were included. A gradient was seen for the effect of ASDAS at t on mSASSS at t+1 (interaction P = 0.10), with a higher progression in patients never treated with TNFi (ß = 0.41 [95% confidence interval (95% CI) 0.13, 0.68]) compared to those continuously treated (ß = 0.16 [95% CI 0.00, 0.31]) (indirect effect). However, TNFi also directly slowed progression, as treated patients had on average an mSASSS 0.85 units lower at t+1 compared to untreated patients (ß = -0.85 [95% CI -1.35, -0.35]). CONCLUSION: Our findings indicate that TNFi reduce spinal radiographic progression in patients with radiographic axial SpA, which might be partially uncoupled from their effects on inflammation as measured by the ASDAS.

Risk of serious infections in arthritis patients treated with biological drugs: a matched cohort study and development of prediction model.

OBJECTIVES: Serious infection is a concern for patients with inflammatory joint diseases treated with biological drugs (bDMARDs). The objectives were to compare risk of serious infection, defined as infection leading to hospitalization, in patients initiating bDMARD treatment with that in the general population and, second, to develop a simple clinical prediction model and to obtain risk estimates for individual patients. METHODS: This was a matched-cohort study based on nationwide registries in Denmark. Patients with RA, axial SpA and PsA initiating first bDMARD monitored in the DANBIO registry were matched 1:10 by age, gender and postal code with controls from the general population. The risk of serious infection during 12 months' follow-up was assessed with Cox regression. Prediction models were developed using logistic regression and compared using area under the receiver operating characteristic curve (AUC). RESULTS: We included 11 372 patients and 113 715 controls. During follow-up, 522 patients (4.6%) and 1434 controls (1.3%) developed a serious infection (hazard ratio 3.7, 95% CI 3.4, 4.1). Age-stratified risk was largely similar across diagnoses. A simple prediction model, the 'DANBIO infection risk score', based on age and a count of six clinical risk factors had moderate discriminative power (internal validation: AUC 0.69) that was comparable to that of the existing RABBIT (Rheumatoide Arthritis Beobachtung der BIologika-Therapie) Risk Score (external validation: AUC 0.68). CONCLUSION: Patients with inflammatory joint diseases initiating bDMARD treatment had a four times increased risk of serious infection compared with the general population. A simple prediction model, feasible for shared decision-making, was developed to obtain risk estimates for individual patients.

Self-protection strategies and health behaviour in patients with inflammatory rheumatic diseases during the COVID-19 pandemic: results and predictors in more than 12 000 patients with inflammatory rheumatic diseases followed in the Danish DANBIO registry.

AIMS: In Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and again after the reopening of the society started. Furthermore, to identify characteristics of patients with high levels of anxiety and self-isolation. METHODS: Patients in routine care followed prospectively in the nationwide DANBIO registry were invited to answer an online questionnaire regarding disease activity and COVID-19 infection, behaviour in March and June 2020. Responses were linked to patient data in DANBIO. Characteristics potentially associated with anxiety, self-isolation and medication adherence (gender/age/diagnosis/education/work status/comorbidity/DMARD/smoking/EQ-5D/disease activity) were explored with multivariable logistic regression analyses. RESULTS: We included 12 789 patients (8168 rheumatoid arthritis/2068 psoriatic arthritis/1758 axial spondyloarthritis/795 other) of whom 65% were women and 36% treated with biological DMARD. Self-reported COVID-19 prevalence was 0.3%. Patients reported that they were worried to get COVID-19 infection (March/June: 70%/45%) and self-isolated more than others of the same age (48%/38%). The fraction of patients who changed medication due to fear of COVID-19 were 4.1%/0.6%. Female gender, comorbidities, not working, lower education, biological treatment and poor European Quality of life, 5 dimensions were associated with both anxiety and self-isolation. CONCLUSION: In >12 000 patients with inflammatory arthritis, we found widespread anxiety and self-isolation, but high medication adherence, in the initial phase of the COVID-19 pandemic. This persisted during the gradual opening of society during the following months. Attention to patients' anxiety and self-isolation is important during this and potential future epidemics.

Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo-Controlled Phase III Study.

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.

Axial involvement in patients with early peripheral spondyloarthritis: a prospective MRI study of sacroiliac joints and spine.

OBJECTIVES: To assess axial involvement on MRI in early peripheral spondyloarthritis (pSpA) and to evaluate whether axial inflammation predicts relapse on treatment withdrawal. METHODS: Fifty-six patients with early, active, newly diagnosed pSpA underwent MRI of the sacroiliac joints (SIJs) and spine prior to golimumab initiation. At sustained clinical remission of pSpA, treatment was withdrawn and a second MRI was performed. Bone marrow oedema (BME) was scored by three readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Scores were compared with an axial spondyloarthritis cohort (Belgian Arthritis and Spondylitis cohort). Structural lesions were assessed using a similar method. Furthermore, fulfilment of the Assessment of Spondyloarthritis International Society (ASAS) definition of a positive MRI for sacroiliitis was assessed. Spinal images were evaluated for BME and structural lesions using the Canada-Denmark MRI spine scoring system by two readers. RESULTS: Thirty-six per cent showed SIJ BME at baseline, all fulfilling the ASAS definition of sacroiliitis. No association with back pain was found. Twenty-one per cent displayed SIJ structural lesions. Spinal BME was limited: the median inflammation scores were low and no patients had ≥5 inflammatory corner lesions. On clinical remission, a significant decrease in SIJ SPARCC scores was detected. On clinical remission, no significant differences in SIJ SPARCC scores were noted between patients relapsing and those maintaining remission after treatment discontinuation. CONCLUSION: In patients with early pSpA, a surprisingly high prevalence of sacroiliitis on MRI was observed; SPARCC scores decreased significantly on tumour necrosis factor inhibition. Residual inflammation on MRI was not predictive of relapse of peripheral manifestations. No relevant inflammatory spinal involvement was detected. Collectively, our findings suggest a higher inflammatory burden in patients with early pSpA than anticipated.