EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Erosions on T1-Weighted Magnetic Resonance Imaging Versus Radiography of Sacroiliac Joints in Recent-Onset Axial Spondyloarthritis: 2-Year Data (EMBARK Trial and DESIR Cohort).

OBJECTIVE: (1) To compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-week 104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); and (2) to compare treatment-discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic axSpA (EMBARK) trial vs controls in the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort. METHODS: Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥ 2 of 3 readers' assessments. RESULTS: At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P < 0.001). After 104 weeks, a decrease in erosions was observed on MRI but not radiographs in 49/221 (22.2%) patients, and on radiographs but not MRI in 6/221 (2.7%) patients (P < 0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, changes in erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedges G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively. CONCLUSION: In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research. [ClinicalTrials.gov: NCT01258738, NCT01648907].

Risk of major adverse cardiovascular events in patients initiating biologics/apremilast for psoriatic arthritis: a nationwide cohort study.

OBJECTIVE: Several biological DMARDs (bDMARDs) have demonstrated anti-inflammatory effects in PsA. However, their comparative cardiovascular safety profiles remain unknown. We evaluated the risk of major adverse cardiovascular events (MACEs) in PsA patients on therapy with different classes of bDMARDs and apremilast. METHODS: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. All adults with PsA who were new users of bDMARDs/apremilast (neither in the year before the index date) during 2015-19 were included. Patients with previous cardiovascular diseases were excluded. End of follow-up was 31 December 2019. The primary endpoint was an occurrence of MACEs in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models. RESULTS: Between 2015 and 2019, we included 9510 bDMARD new users [mean age 48.5 (s.d. 12.7) years; 42% men], including 7289 starting a TNF inhibitor, 1058 an IL-12/23 inhibitor and 1163 an IL-17 inhibitor, with 1885 apremilast new users [mean age 54.0 (s.d. 12.5) years; 44% men]. MACEs occurred in 51 (0.4%) patients. After propensity score weighting, the risk of MACEs was significantly greater with IL-12/23 (weighted hazard ratio 2.0, 95% CI 1.3, 3.0) and IL-17 (weighted hazard ratio 1.9, 95% CI 1.2, 3.0) inhibitors than TNF inhibitors, with no significant increased risk with apremilast (weighted hazard ratio 1.3, 95% CI 0.8, 2.2). Similar results were observed with the Fine-Gray competing risks survival model. CONCLUSION: Analysis of a large database revealed a small overall number of MACEs, and the risk of MACEs was greater for PsA new users of IL-12/23 and IL-17 vs TNF inhibitors.

Factors associated with remission at 5-year follow-up in recent-onset axial spondyloarthritis: results from the DESIR cohort.

OBJECTIVE: The factors contributing to long-term remission in axial SpA (axSpA) are unclear. We aimed to characterize individuals with axSpA at the 5-year follow-up to identify baseline factors associated with remission. METHODS: We included all patients from the DESIR cohort (with recent-onset axSpA) with an available Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP < 1.3) were compared with those with active disease by demographic, clinical, biological and imaging characteristics. A logistic model stratified on TNF inhibitor (TNFi) exposure was used. RESULTS: Overall, 111/449 patients (25%) were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared with 17% (34/202) of those exposed to TNFi. Patients in remission after 5 years were more likely to be male, HLA-B27+, have a lower BMI, and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi included lower BASDAI [adjusted odds ratio (ORa) 0.9, 95% CI: 0.8, 0.9) and history of peripheral arthritis (ORa 2.1, 95% CI: 1.2, 5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95% CI: 1.6, 5.1), lower enthesitis index (ORa 0.8, 95% CI: 0.7, 0.9), lower BASDAI (ORa 0.9, 95% CI: 0.9, 0.9) and lower BMI (ORa 0.8, 95% CI: 0.7, 0.9). CONCLUSION: This study highlights the difficulty in achieving 5-year remission in those with recent-onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.

New-onset inflammatory bowel diseases among IL-17 inhibitor-treated patients: results from the case-control MISSIL study.

OBJECTIVES: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. METHODS: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. RESULTS: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. CONCLUSION: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Paradoxical reactions and biologic agents: a French cohort study of 9303 patients.

BACKGROUND: Paradoxical reactions (PRs) are defined as the occurrence during biologic therapy of a pathological condition that usually responds to these drugs. OBJECTIVES: To estimate the incidence of PRs and identify risk factors. METHODS: Multicentre study of the database for the Greater Paris University Hospitals, including biologic-naive patients receiving anti-tumour necrosis factor-α, anti-interleukin-12/23, anti-interleukin-17 or anti-α4ß7-integrin agents for psoriasis, inflammatory rheumatism or inflammatory bowel disease (IBD). We used natural language processing algorithms to extract data. A cohort and a case-control study nested in the cohort with controls selected by incidence density sampling was used to identify risk factors. RESULTS: Most of the 9303 included patients (median age 43·0, 53·8% women) presented an IBD (3773, 40·6%) or a chronic inflammatory rheumatic disease (3708, 39·9%), and 8489 (91·3%) received anti-TNF-α agents. A total of 297 (3·2%) had a PR. The global incidence rate was 7·6 per 1000 person-years [95% confidence interval (CI) 6·8-8·5]. The likelihood of PR was associated with IBD [adjusted odds ratio (aOR) 1·9, 95% CI 1·1-3·2, P = 0·021] and a combination of at least two inflammatory diseases (aOR 6·1, 95% CI 3·6-10·6, P < 0·001) and was reduced with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and corticosteroids (aOR 0·6, 95% CI 0·4-0·8, P = 0·002; and OR 0·4, 95% CI 0·2-0·6, P = 0·002, respectively). CONCLUSIONS: The likelihood of PRs was associated with IBD or a combination of a least two inflammatory diseases. More studies are needed to assess the benefit of systematically adding csDMARDs for such high-risk patients. What is already known about this topic? Most published studies about paradoxical reactions concern paradoxical psoriasis in patients receiving anti-tumour necrosis factor-α agents. Few data are available for other paradoxical reactions and the most recent biologics. What does this study add? Risk of paradoxical reactions was increased with inflammatory bowel disease and a combination of at least two inflammatory diseases. Risk of paradoxical reactions was reduced with conventional synthetic disease-modifying antirheumatic drugs or corticosteroid therapy, which could be added for high-risk patients.

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.

Epidemiologic study of patients with psoriatic arthritis in a real-world analysis: a cohort study of the French health insurance database.

OBJECTIVE: PsA is a chronic inflammatory arthritis with heterogeneous disease manifestations. Data on the prevalence of PsA in adults differ widely depending on the study and the country. This study aimed to estimate the prevalence and incidence of PsA in France, characterize comorbidities associated to PsA and identify prescribed treatments. METHODS: This nationwide cohort study involved the administrative healthcare database (Système National des Données de Santé) of the French health insurance scheme linked to the national hospital discharge database. All adults with PsA registered in the database and identified with a specific International Classification of Diseases, 10th revision code (M07) were included between 1 January 2015 and 31 December 2018. RESULTS: A total of 63 598 patients were identified as having PsA [55.9 years (s.d. 14.4), 45.6% males]. The prevalence of PsA was estimated at 0.1% and the incidence at 8.4 per 100 000 person-years in the general population. The most common comorbidities were hypertension, diabetes, chronic obstructive pulmonary disease and dyslipidaemia. The prevalence of treatment with conventional synthetic DMARDs (csDMARDs), biological or biosimilar DMARDs (b/bsDMARDs) and apremilast for PsA was 25.9% (16 453), 30.4% (19 325) and 3.5% (2231), respectively. Overall, 8966 (14.1%) patients were new users of csDMARDs, 8311 (13.1%) were new users of b/bsDMARDs and 1529 (7.4%) were new users of apremilast. The most common first-line csDMARD was methotrexate (70.9%) and the most frequent first-line b/bsDMARD was adalimumab (30.8%). CONCLUSION: Our results lead to a better understanding of PsA. Results were similar to those from other published studies using other data sources, which highlights the reliability of insurance databases for studies.

Evaluation of the impact of a nurse-led program of patient self-assessment and self-management in axial spondyloarthritis: results of a prospective, multicentre, randomized, controlled trial (COMEDSPA).

OBJECTIVE: To evaluate the impact of a nurse-led program of self-management and self-assessment of disease activity in axial spondyloarthritis. METHODS: Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants were consecutive axial spondyloarthritis patients (according to the rheumatologist) and nurses having participated in a 1-day training meeting. The program included self-management: educational video and specific video of graduated, home-based exercises for patients; and self-assessment: video presenting the rationale of tight monitoring of disease activity with composite scores (Ankylosing Spondylitis Disease activity Score, ASDAS/Bath Ankyslosing Spondylitis Disease Activity Index, BASDAI). The nurse trained patients to collect, calculate and report (monthly) ASDAS/BASDAI. Treatment allocation was by random allocation to this program or a comorbidities assessment (not presented here and considered here as the control group). RESULTS: A total of 502 patients (250 and 252 in the active and control groups, respectively) were enrolled (age: 46.7 (12.2) years, male gender: 62.7%, disease duration: 13.7 (11.0) years). After the one-year follow-up period, the adherence to the self-assessment program was considered good (i.e. 79% reported scores >6 times). Despite a lack of statistical significance in the primary outcome (e.g. coping) there was a statistically significant difference in favor of this program for the following variables: change in BASDAI, number and duration of the home exercises in the active group, and physical activity (international physical activity score, IPAQ). CONCLUSION: This study suggests a short-term benefit of a nurse-led program on self-management and self-assessment for disease activity in a young axial spondyloarthritis population in terms of disease activity, exercises and physical activity.

Secukinumab and ustekinumab treatment in psoriatic arthritis: results of a direct comparison.

OBJECTIVES: To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. METHODS: In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. RESULTS: A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. CONCLUSION: In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

Clinical manifestations, disease activity and disease burden of radiographic versus non-radiographic axial spondyloarthritis over 5 years of follow-up in the DESIR cohort.

OBJECTIVES: To compare the clinical manifestations, disease activity and disease burden between patients with radiographic (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) over a 5-year follow-up period in the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort. METHODS: Patients from the DESIR cohort who had X-ray images of the sacroiliac joints available at baseline and did not leave the study during the 5-year follow-up period because of a diagnosis other than axSpA were included. A unilateral rating of 'obvious sacroiliitis' by the local reader was considered sufficient for classification as r-axSpA. The incidence of first episodes of peripheral and extra-rheumatic manifestations was compared between the two groups using the incidence rate ratio and Cox regressions adjusted for sex, age and tumour necrosis factor blocker (TNFb) intake. Mean values of patient-reported outcomes (PROs) and days of sick leave over 5 years of follow-up were compared using mixed models adjusted for sex, age, TNFb intake and baseline values. RESULTS: In total, 669 patients were included, of whom 185 (27.7%) and 484 (72.3%) were classified as r-axSpA and nr-axSpA, respectively. At baseline, the r-axSpA patients showed a significantly higher prevalence of males. After adjusting for age, sex and TNFb intake, Cox regressions for peripheral and extra-rheumatic manifestations did not show any significant differences between groups. Mixed models also showed similar mean levels in PROs and days of sick leave between groups over time. CONCLUSION: The incidence of peripheral and extra-rheumatic manifestations as well as the disease burden over time remained similar between r-axSpA and nr-axSpA groups after adjusting for intermediate variables. TRIAL REGISTRATION NUMBER: NCT01648907.

Spinal-pelvic orientation: potential effect on the diagnosis of spondyloarthritis.

OBJECTIVE: To assess associations of spinal-pelvic orientation with clinical and imaging-study findings suggesting axial SpA (axSpA) in patients with recent-onset inflammatory back pain. METHODS: Spinal-pelvic orientation was assessed in DESIR cohort patients with recent-onset inflammatory back pain and suspected axSpA, by using lateral lumbar-spine radiographs to categorize sacral horizontal angle (<40° vs ⩾40°), lumbosacral angle (<15° vs ⩾15°) and lumbar lordosis (LL, <50° vs ⩾50°). Associations between these angle groups and variables collected at baseline and 2 years later were assessed using the χ2 test (or Fisher's exact) and the Mann-Whitney test. With Bonferroni's correction, P < 0.001 indicated significant differences. RESULTS: Of 362 patients, 358, 356 and 357 had available sacral horizontal angle, lumbosacral angle and LL values, respectively; means were 39.3°, 14.6° and 53.0°, respectively. The prevalence of sacroiliitis on both radiographs and MRI was higher in the LL < 50° group than in the LL ⩾50° group, but the difference was not statistically significant. Clinical presentation and confidence in a diagnosis of axSpA did not differ across angle groups. No significant differences were identified for degenerative changes according to sacral horizontal angle, lumbosacral angle or LL. CONCLUSION: Spinal-pelvic balance was not statistically associated with the clinical or imaging-study findings suggesting axSpA in patients with recent-onset inflammatory back pain.

Clinical peripheral enthesitis in the DESIR prospective longitudinal axial spondyloarthritis cohort.

OBJECTIVES: We aimed to describe the prevalence and characteristics of peripheral enthesitis in recent onset axial spondyloarthritis, estimate the incidence of peripheral enthesitis over time, and determine the factors associated with the presence of peripheral enthesitis. METHODS: 708 patients with recent onset axial spondyloarthritis were enrolled in the DESIR cohort ( prospective multi-centre, longitudinal). Data regarding the patients and spondyloarthritis characteristics at baseline with a specific focus on enthesitis and occurrence of peripheral enthesitis were collected during the five years of follow-up. RESULTS: At inclusion, 395 patients (55.8%) reported peripheral enthesitis. The locations were mainly the plantar fascia (53.7%) and the Achilles tendon (38.5%). During the 5-year follow-up period, 109 additional patients developed peripheral enthesitis resulting in an estimated (Kaplan-Meier method) percentage of 71% (95% CI: 68-75). Variables associated with peripheral enthesitis in the univariate analysis were: older age, male gender, absence of HLA B27, MRI sacroiliitis and fulfilled Modified NY criteria, presence of anterior chest wall pain, peripheral arthritis, dactylitis, psoriasis, high BASDAI, BASFI, mean score ASAS-and the use of NSAIDs. Only the history of anterior chest wall pain and of peripheral arthritis were retained in the multivariate analysis (odds ratio (OR)=1.6 [95% confidence interval [1.1-2.3], and OR=2.1 [1.4-3.0], respectively). CONCLUSIONS: This study highlights the high prevalence of peripheral enthesitis in recent onset axial spondyloarthritis, and suggests that in combination with peripheral arthritis, enthesitis might have an impact on the burden of the disease.

Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers' effectiveness in axial spondyloarthritis: results of a prospective, multicentre study.

OBJECTIVE: To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers' (TNFb) response. DESIGN: Prospective observational study with two visits 3 months apart. PATIENTS: Adult patients with AxSpa initiating a TNFb. STUDY GROUPS: FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM. STATISTICAL ANALYSIS: Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response. RESULTS: Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups. CONCLUSION: This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients.

Evaluation of the change in structural radiographic sacroiliac joint damage after 2 years of etanercept therapy (EMBARK trial) in comparison to a contemporary control cohort (DESIR cohort) in recent onset axial spondyloarthritis.

OBJECTIVE: To compare 2 years of radiographic sacroiliac joint (SIJ) changes in patients with recent onset axial spondyloarthritis (axSpA) receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). METHODS: Endpoints were changes at week 104 per the modified New York (mNY) grading system in total SIJ score (primary endpoint) and net percentage of patients with progression defined three ways. Treatment effect was analysed with and without adjustment for baseline covariates. RESULTS: At 104 weeks, total SIJ score improved in the etanercept group (n=154, adjusted least-squares mean change: -0.14) and worsened in the control group (n=182, change: 0.08). The adjusted difference between groups (etanercept minus control) was -0.22 (95% CI -0.38 to -0.06), p=0.008. The net percentage of patients with progression was significantly lower in the etanercept versus the control group for two of three binary endpoints: -1.9% versus 1.6% (adjusted difference for etanercept minus control: -4.7%,95% CI -9.9 to 0.5, p=0.07) for change in mNY criteria; -1.9% versus 7.8% (adjusted difference: -18.2%,95% CI -30.9 to -5.6, p=0.005) for change ≥1 grade in ≥1 SIJ; and -0.6% versus 6.7% (adjusted difference: -16.4%,95% CI -27.9 to -5.0, p=0.005) for change ≥1 grade in ≥1 SIJ, with shift from 0 to 1 or 1 to 0 considered no change. CONCLUSION: Despite the slow radiographic SIJ progression rate over 2 years in axSpA, this study suggests a lower rate of progression in the SIJ with etanercept than without anti-tumour necrosis factor therapy. TRIAL REGISTRATION NUMBERS: NCT01258738, NCT01648907; Post-results.

Which scoring method depicts spinal radiographic damage in early axial spondyloarthritis best? Five-year results from the DESIR cohort.

Objective: To compare the performance of different spinal radiographic damage scoring methods in patients with early axial spondyloarthritis (axSpA). Methods: Five-year spinal radiographs from the DESIR cohort were scored by three readers (averaged) for the calculation of the Stoke AS Spine Score (SASSS), modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Radiographic AS Spinal Score (RASSS), BASRI-spine and BASRI-total, and following the OMERACT filter, scores were compared according to truth, discrimination (reliability and sensitivity to change) and feasibility. The proportion of patients with a net change > smallest detectable change and >1 was calculated. The proportion of total variance explained by the patient (true variance) was calculated for the change scores as a measure of reliability, using analysis of variance. Results: In total 699 patients were included. Five-year net changes > smallest detectable change (>1) were: RASSS 17% (17%), mSASSS 12% (12%), BASRI-spine and BASRI-total 12% (9%), SASSS 11% (11%). The mSASSS and the RASSS performed the best in terms of capturing the signal (positive change) related to noise (negative change). The proportion of variance explained by the patient was highest for the mSASSS and RASSS (85% for both 5-year progression scores vs 50-55% for other methods). The proportion of patient variance in the thoracic segment of the RASSS was unsatisfactory (46% for progression). Conclusion: The existing scoring methods to assess spinal radiographic damage performed well in early phases of axSpA. The mSASSS and RASSS captured most change. There was no clear gain in additionally scoring the thoracic spine for the RASSS. The mSASSS remains the most sensitive and valid scoring method in axSpA, including early phases of the disease.

Evaluation of extreme patient-reported outcome in early spondyloarthritis and its impact on the effect of TNF-α blockers treatment.

OBJECTIVES: To describe the prevalence of extreme patient-reported outcomes (PRO) in an early axial spondyloarthritis setting, to compare the phenotype of patients with/without extreme PRO and to evaluate the impact of extreme PRO on the effectiveness of TNF-α blockers (TNFb). METHODS: This analysis was performed in the DESIR cohort. Extreme PRO were measured at baseline and were defined as a score ≥8 on at least three of first five BASDAI items. Phenotype of patient's with/without extreme PRO was compared. Impact of extreme PRO on TNFb effectiveness was evaluated by comparing the retention rate of the first TNFb in both groups by survival curves analysis (log-rank and Cox analysis). RESULTS: Extreme PRO were present in 95 out of the 708 patients (13.4%). Patients with extreme PRO were older (mean (SD) age of 35.4(8.6) years vs. 33.5(8.7) years), more frequently females (65.3% vs. 51.9%), had higher BASDAI (7.1 vs. 4.1), reported more frequently history of depression (25.3% vs. 10.2%) and use of anti-depressive drugs (19.0% vs. 7.2%). TNFb treatment was more frequently initiated in the extreme PRO group (48.4% vs. 25.5%), while the proportion of patients still on TNFb at 2 years was significantly lower in the extreme PRO group 18.6% (n=8) vs. 39.5% (n=60). Presence of extreme PRO was independently associated with first TNFb discontinuation (HR 1.8, [95% CI 1.2;2.9], p=0.01)). CONCLUSIONS: Although presence of extreme PRO in this early axSpA setting was not very frequent, patients with extreme PRO were more likely to receive a TNFb and less likely to maintain the treatment at 2 years. Further studies evaluating the specific impact of extreme PRO on TNFb treatment in axSpA are warranted.