The ASAS-OMERACT core domain set for axial spondyloarthritis.

BACKGROUND: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary. OBJECTIVE: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA). METHODS: Following OMERACT and COMET guidelines, an international working group representing key stakeholders (patients, rheumatologists, health professionals, pharmaceutical industry and drug regulatory agency representatives) defined the core domain set for axSpA. The development process consisted of: i) Identifying candidate domains using a systematic literature review and qualitative studies; ii) Selection of the most relevant domains for different stakeholders through a 3-round Delphi survey involving axSpA patients and axSpA experts; iii) Consensus and voting by ASAS; iv) Endorsement by OMERACT. Two scenarios are considered based on the type of therapy investigated in the trial: symptom modifying therapies and disease modifying therapies. RESULTS: The updated core outcome set for axSpA includes 7 mandatory domains for all trials (disease activity, pain, morning stiffness, fatigue, physical function, overall functioning and health, and adverse events including death). There are 3 additional domains (extra-musculoskeletal manifestations, peripheral manifestations and structural damage) that are mandatory for disease modifying therapies and important but optional for symptom modifying therapies. Finally, 3 other domains (spinal mobility, sleep, and work and employment) are defined as important but optional domains for all trials. CONCLUSION: The ASAS-OMERACT core domain set for AS has been updated into the ASAS-OMERACT core domain set for axSpA. The next step is the selection of instruments for each domain.

Spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison.

OBJECTIVE: The aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS). METHODS: Baseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31-743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640-819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs. RESULTS: A total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant. CONCLUSION: Secukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

Is it Useful to Repeat Magnetic Resonance Imaging of the Sacroiliac Joints After Three Months or One Year in the Diagnosis of Patients With Chronic Back Pain and Suspected Axial Spondyloarthritis?

OBJECTIVE: To investigate the value of repeated magnetic resonance imaging (MRI) of the sacroiliac (SI) joints in diagnosing chronic back pain patients in whom axial spondyloarthritis (SpA) is suspected and to examine determinants of positive MRI findings in SI joints. METHODS: Patients with chronic back pain (duration 3 months-2 years, age ≥16 years, age at onset <45 years) with ≥1 SpA feature who were included in the Spondyloarthritis Caught Early cohort underwent visits at baseline, at 3 months, and at 1 year. Visits included an evaluation of all SpA features and repeated MRI of SI joints. MRI-detected axial SpA positivity (according to the definition from the Assessment of SpondyloArthritis international Society) was evaluated by 2 or 3 well-trained readers who were blinded with regard to clinical information. The likelihood of a positive MRI finding at follow-up visits (taking into consideration contributing factors) was calculated by generalized estimating equation analysis. RESULTS: Of the 188 patients, 38.3% were male, the mean ± SD age was 31.0 ± 8.2 years, and the mean ± SD symptom duration was 13.2 ± 7.1 months. Thirty-one patients (16.5%) had positive MRI findings in the SI joints at baseline. After 3 months and after 1 year, the MRI results had changed from positive to negative in 3 of 27 patients (11.1%) and 11 of 29 patients (37.9%), respectively, which was attributable in part to the initiation of anti-tumor necrosis factor therapy. Status changes from negative to positive were seen in 5 of 116 patients (4.3%) after 3 months and in 10 of 138 patients (7.2%) after 1 year. HLA-B27 positivity and male sex were independent determinants of the likelihood of a positive MRI scan at any time point (42% in HLA-B27+ men and 6% in HLA-B27- women). If the baseline results were negative, the likelihood of a positive scan at follow-up was very low (≤7%). CONCLUSION: MRI-detected status changes in the SI joints were seen in a minority of the patients, and both male sex and HLA-B27 positivity were important predictors of MRI positivity. Our findings indicate that conducting MRI scans after 3 months or after 1 year in patients with suspected early axial SpA is not diagnostically useful.

Performance of the Michigan Hand Outcomes Questionnaire in hand osteoarthritis.

OBJECTIVE: To investigate the performance of the Michigan Hand Outcomes Questionnaire (MHQ) in hand osteoarthritis (OA) by evaluating truth, discrimination and feasibility. DESIGN: Symptomatic hand OA patients from the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort completed questionnaires (demographics, MHQ, Australian/Canadian Hand Osteoarthritis Index [AUSCAN], Functional Index for Hand Osteoarthritis [FIHOA] and visual analogue scale [VAS] pain) at baseline (n = 383), 1- and 2-year follow-up (n = 312, n = 293). Anchor questions at follow-up assessed whether pain/function levels were (un)acceptable and had changed compared to baseline. Correlations between MHQ and other pain/function questionnaires were calculated. Validity of unique MHQ domains (work performance, aesthetics, satisfaction), discrimination across disease stages, and responsiveness were assessed by categorizing patients by external anchors (employment, joint deformities, erosions, and anchor questions). Between-group differences were assessed with linear regression, probability plots and comparison of medians. RESULTS: MHQ pain and function subscales correlated moderately-to-good with other instruments (rs 0.63-0.81). Work performance scores were worse in patients with reduced working capacity than in employed patients. Aesthetics scores were worse in patients with more deformities. Patients with unacceptable complaints had worse satisfaction scores. All pain/function instruments discriminated between patients with acceptable vs unacceptable pain/function, while only MHQ activities of daily living (ADL), FIHOA, and MHQ aesthetics could discriminate between erosive and non-erosive disease. MHQ and AUSCAN were most responsive. CONCLUSIONS: MHQ has several unique aspects and advantages justifying its use in hand OA, including the unique assessment of work performance, aesthetics, and satisfaction. However, MHQ, AUSCAN and FIHOA appear to measure different aspects of pain and function.

Association of Comorbidities in Spondyloarthritis With Poor Function, Work Disability, and Quality of Life: Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study.

OBJECTIVE: Comorbidities add to the burden of disease and its complexity, and may prevent the achievement of treat-to-target goals. The objective of this study was to study the relationship between comorbidities and key disease outcomes in spondyloarthritis (SpA), namely function, work ability, and quality of life. METHODS: Patients from the multinational (22 countries), cross-sectional Assessment in SpondyloArthritis international Society (ASAS) Comorbidities in Spondyloarthritis study were included in the analysis, provided they fulfilled the ASAS criteria. Data on comorbidities based on both self- and physician-report were collected through questionnaires and were subsequently used to compute the Rheumatic Disease Comorbidity Index (RDCI). Univariable and multivariable (adjusted for relevant confounders) multilevel (with country as a random effect) linear or logistic (as appropriate) regression analyses were conducted to investigate the relationship between the RDCI and functional ability, work ability, and quality of life. RESULTS: In total, 3,370 of 3,984 recruited patients (85%) fulfilled the ASAS criteria: 66% were male, mean ± SD age was 43 ± 14 years, mean ± SD disease duration was 8.4 ± 9.5 years, and mean ± SD RDCI was 0.7 ± 1.1. At least 1 comorbidity was reported in 51% of patients; 9% had ≥3 comorbidities. RDCI was independently associated with a higher Bath Ankylosing Spondylitis Functional Index score (ß = 0.37, 95% confidence interval [95% CI] 0.30, 0.43), lower EuroQol 5-domain questionnaire (ß = -0.03, 95% CI -0.04, -0.02), less work employment (odds ratio [OR] 0.83, 95% CI 0.76, 0.91), higher absenteeism (OR 1.18, 95% CI 1.04, 1.34), and higher presenteeism (OR 1.42, 95% CI 1.26, 1.61). CONCLUSION: Comorbidities in SpA adversely influence physical function, work ability, and quality of life and are important to take into account in daily clinical practice.

Prevalence and clinical significance of lumbosacral transitional vertebra (LSTV) in a young back pain population with suspected axial spondyloarthritis: results of the SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVE: To determine in a cohort of young patients with suspected axial spondyloarthritis (axSpA), the prevalence of lumbosacral transitional vertebra (LSTV), its association with local bone marrow edema (BME) and lumbar spine degeneration, and the potential relationship with MRI findings and clinical signs of axSpA. MATERIALS AND METHODS: Baseline imaging studies and clinical information of patients from the SPondyloArthritis Caught Early-cohort (back pain ≥3 months, ≤2 years, onset <45 years) were used. Two independent readers assessed all patients for LSTV on radiography, and BME-like and degenerative changes on MRI. Patients with and without LSTV were compared with regard to the prevalence of MRI findings and the results of clinical assessment using Chi-squared test or t test. RESULTS: Of 273 patients (35.1% male, mean age 30.0), 68 (25%) patients showed an LSTV, without statistical significant difference between patients with and without axSpA (p = 0.327). Local sacral BME was present in 9 out of 68 (13%) patients with LSTV and absent in patients without LSTV (p < 0.001). Visual analogue scale (VAS) pain score and spinal mobility assessments were comparable. CONCLUSIONS: LSTV is of low clinical relevance in the early diagnosis of axSpA. There is no difference between patients with and without LSTV regarding the prevalence of axSpA, pain and spinal mobility, and a BME-like pattern at the pseudoarticulation does not reach the SI joints.

Presence of multiple spondyloarthritis (SpA) features is important but not sufficient for a diagnosis of axial spondyloarthritis: data from the SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVES: Concerns have been raised about overdiagnosis of axial spondyloarthritis (axSpA). We investigated whether patients with chronic back pain (CBP) of short duration and multiple SpA features are always diagnosed with axSpA by the rheumatologist, and to what extent fulfilment of the Assessment of SpondyloArthritis International Society (ASAS) axSpA criteria is associated with an axSpA diagnosis. METHODS: Baseline data from 500 patients from the SPondyloArthritis Caught Early cohort which includes patients with CBP (≥3 months, ≤2 years, onset <45 years) were analysed. All patients underwent full diagnostic workup including MRI of the sacroiliac joints (MRI-SI) and radiograph of sacroiliac joints (X-SI). For each patient, the total number of SpA features excluding sacroiliac imaging and human leucocyte antigen B27 (HLA-B27) status was calculated. RESULTS: Before sacroiliac imaging and HLA-B27 testing, 32% of patients had ≤1 SpA feature, 29% had 2 SpA features, 16% had 3 SpA features and 24% had ≥4 SpA features. A diagnosis of axSpA was made in 250 (50%) of the patients: 24% with ≤1 SpA feature, 43% with 2 SpA features, 62% with 3 SpA features and 85% with ≥4 SpA features. Of the 230 patients with a positive ASAS classification 40 (17.4%) did not have a diagnosis of axSpA. HLA-B27 positivity (OR 5.6; 95% CI 3.7 to 8.3) and any (MRI-SI and/or X-SI) positive imaging (OR 34.3; 95% CI 17.3 to 67.7) were strong determinants of an axSpA diagnosis. CONCLUSIONS: In this cohort of patients with CBP, neither the presence of numerous SpA features nor fulfilment of the ASAS classification criteria did automatically lead to a diagnosis axSpA. Positive imaging was considered particularly important in making a diagnosis of axSpA.

Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study.

OBJECTIVES: To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks. METHODS: DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints. RESULTS: Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): -1.00 vs -0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY). CONCLUSIONS: CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX. TRIAL REGISTRATION NUMBER: NCT01519791.

Illness Perceptions and Outcomes in Patients with Inflammatory Bowel Disease: Is Coping a Mediator?

PURPOSE: Patients with inflammatory bowel disease (IBD) often experience severe impairment in different life domains. Psychological factors, such as illness perceptions and coping, may play a role in the adjustment to IBD as indicated by mental and physical health, activity, and work impairment. The present study aimed at examining the assumption of the Common Sense Model (CSM) that coping mediates the relationship between illness perceptions and adjustment in patients with IBD. METHOD: In a cross-sectional design, 211 IBD patients (73 % Crohn's disease, 40 % male, mean age 42.9 ± 12.9 years) attending an outpatient clinic completed questionnaires assessing illness perceptions (IPQ-R), coping (CORS), mental and physical health (SF-36), as well as activity and work impairment (WPAI). Multiple mediation analyses were applied that allow estimating the total and direct effects of all illness perception dimensions and the indirect effects through all coping strategies on the illness outcomes simultaneously. RESULTS: The analyses yielded significant direct effects of perceptions regarding the cyclical course, the chronic course, the severity of the consequences, the comprehensibility, and the emotional impact of IBD on study outcomes. Additionally, significant indirect effects were found for the perceptions regarding the severity of the consequences, the possibility of personal control, and the comprehensibility of IBD on mental and physical health as well as activity impairment through the use of one specific coping strategy, i.e., reduction of activity. CONCLUSION: The results provide evidence for the assumptions of the CSM and suggest the importance of addressing illness perceptions and activity stimulation in quality health care for IBD patients.

Early Disease Activity or Clinical Response as Predictors of Long-Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis.

OBJECTIVE: Early identification of patients unlikely to achieve good long-term disease control with anti-tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat-to-target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol. METHODS: The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week-48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID-axSpA and RAPID-PsA trial data. RESULTS: A clear relationship between disease activity from week 2 to 12 and achievement of week-48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week-48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week-12 ASDAS inactive disease. For PsA, week-48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28-CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week-48 outcomes, though to a lesser extent than disease activity. CONCLUSION: Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long-term treatment goals.

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages.

INTRODUCTION: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. METHODS: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. RESULTS: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. DISCUSSION: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.

Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.

OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

Are Additional Tests Needed to Rule Out Axial Spondyloarthritis in Patients Ages 16-45 Years With Short-Duration Chronic Back Pain and Maximally One Spondyloarthritis Feature?

OBJECTIVE: To investigate whether HLA-B27 testing and imaging of the sacroiliac joints are needed in patients with ≤1 spondyloarthritis (SpA) feature, referred to a secondary care setting, after medical history collection, clinical examination, and measurement of acute phase reactants. METHODS: Baseline data from patients in the Spondyloarthritis Caught Early (SPACE) cohort visiting the rheumatology outpatient clinic of 5 centers across Europe (with back pain ≥3 months, ≤2 years, onset at ages <45 years) were used. All patients underwent a full diagnostic work-up: magnetic resonance imaging (MRI) and radiographs of the sacroiliac joints, HLA-B27 testing, and assessment of all other SpA features. Patients were diagnosed according to the treating rheumatologist and classified according to the Assessment of SpondyloArthritis international Society (ASAS) axial SpA criteria. RESULTS: Of the 354 patients, 133 (37.5%) showed 0 or 1 SpA feature after medical history collection, physical examination, and measurement of acute phase reactants (38 without SpA features, 95 with 1 SpA feature). Of the patients with ≤1 SpA feature, 18.4% (with 0 SpA features) and 17.9% (with 1 SpA feature) were diagnosed with axial SpA according to the rheumatologist after additional investigations (HLA-B27 testing and sacroiliac joint imaging). Additionally, 4 of 38 patients (10.5%) without SpA features fulfilled the ASAS axial SpA criteria (all according to the imaging arm only: 2 as MRI+/modified New York criteria (mNY)+, 1 as MRI+/mNY-, and 1 as MRI-/mNY+). Of the 95 patients with 1 SpA feature, 22 (23.2%) fulfilled the ASAS axial SpA criteria (all according to the imaging arm only: 3 as MRI+/mNY+, 15 as MRI+/mNY-, and 4 as MRI-/mNY+). CONCLUSION: In these patients in a secondary care setting with ≤1 SpA feature, axial SpA could not be ruled out without sacroiliac joint imaging and/or HLA-B27 testing.

Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis.

OBJECTIVE: Axial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID-axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA. METHODS: The RAPID-axSpA (NCT01087762) trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose-blind phase were re-randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient-years. RESULTS: At baseline, 38 of 218 CZP-randomized patients (17.4%) and 31 of 107 placebo-randomized patients (29.0%) had past uveitis history. During the 24-week double-blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6-8.8] per 100 patient-years) than in placebo (10.3 [95% CI 2.8-26.3] per 100 patient-years). All cases observed during the 24-week double-blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5-50.1] per 100 patient-years) than placebo (38.5 [95% CI 10.5-98.5] per 100 patient-years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2-7.4] per 100 patient-years) and were similar between AS (4.4 [95% CI 2.3-7.7] per 100 patient-years) and nr-axial SpA (5.6 [95% CI 2.9-9.8] per 100 patient-years). CONCLUSION: The rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti-tumor necrosis factor antibodies.

Signal intensity loss of the intervertebral discs in the cervical spine of young patients on fluid sensitive sequences.

OBJECTIVE: To evaluate the signal intensity (SI) of the intervertebral discs of the cervical spine on magnetic resonance (MR) fluid sensitive sequences, and correlate this to secondary signs of degeneration on MR and radiographs as well as to age. MATERIAL AND METHODS: A total of 265 patients aged ≥16 with back pain (≥3-months, <2-year, onset <45-years) from the SPondyloArthritis Caught Early (SPACE) cohort were included. Sagittal 1.5 T MR images and lateral radiographs of the cervical spine were independently evaluated by two readers for: SI of the intervertebral discs using a grading system based of Pfirrmann (grade 1 normal/bright SI; 2 inhomogeneous/bright SI; 3 inhomogeneous/mildly decreased SI; 4 inhomogeneous/markedly decreased SI; 5 signal void), disc herniation and Modic changes (MRI) and disc space narrowing, osteophytes and sclerosis (radiograph). Readers were blinded for clinical information. Descriptive statistics were used for characteristics and prevalence of findings, and regression analysis was used for age and grades. RESULTS: Of 265 patients (36% male, mean age 30), 221 (83%) patients had 1 to 6 discs (median 4) with decreased SI. Of 1,590 discs, 737 (46%) were grade 1; 711 (45%) grade 2; 133 (8%) grade 3; 8 (1%) grade 4 and 1 (0%) grade 5. Secondary signs of degeneration were rare and seen predominantly in C5-C7 and appear to be related to signal loss grade 3 and 4. CONCLUSION: Low signal intensity of intervertebral discs in absence of secondary degenerative signs in the cervical spine on fluid sensitive MR images might be pre-existing and part of the natural course.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Work Outcome in Patients With Ankylosing Spondylitis: Results From a 12-Year Followup of an International Study.

OBJECTIVE: To understand the impact of ankylosing spondylitis (AS) on work disability (WD) over 12 years compared with the general population, and explore factors predicting adverse work outcome, defined as new partial WD or reduction in working hours. METHODS: Source of data was the Outcome Assessments in Ankylosing Spondylitis International Study, which includes patients from The Netherlands, France, and Belgium. Standardized WD rates over time compared to the general population were calculated using indirect standardization (Dutch patients only). Cox survival analyses identified baseline predictors as well as time-varying factors influencing adverse work outcome over 12 years. RESULTS: Of 215 patients, 55 (26%) were full WD at baseline and 139 (65%) were at risk for adverse work outcome during followup. When compared to the general population, WD over 12 years continued to be increased in Dutch men (incidence rate [IR] 2.9 [95% confidence interval (95% CI) 1.2, 4.6]), but less clearly for women (IR 1.2 [95% CI -0.4, 2.9]). Within the entire sample, baseline predictors of adverse work outcome over 12 years were residence in The Netherlands (versus France or Belgium) (hazard ratio [HR] 3.4 [95% CI 1.4, 8.4]) and worse Bath Ankylosing Spondylitis Functional Index (BASFI) (HR 1.2 [95% CI 1.0, 1.4]). Time-varying predictors over 12 years were residence in The Netherlands, uveitis, and either BASFI or Bath Ankylosing Spondylitis Disease Activity Index with age and inflammatory bowel disease. CONCLUSION: Although WD was already prevalent at inclusion in the cohort, a substantial proportion of patients incurred further adverse work outcome over 12 years. In addition to country of residence, uveitis, age, and self-reported physical function or disease activity predicted long-term adverse work outcome.

Classifying Back Pain and Peripheral Joint Complaints in Inflammatory Bowel Disease Patients: A Prospective Longitudinal Follow-up Study.

BACKGROUND AND AIMS: Peripheral joint complaints [pJTC] and chronic back pain [CBP] are the most common extra-intestinal manifestations in patients with inflammatory bowel disease [IBD]. This prospective study evaluates variables associated with joint/back pain, including IBD disease activity. METHODS: IBD patients with back pain ≥ 3 months and/or peripheral joint pain/swelling [n = 155], and IBD patients without joint complaints [n = 100; controls], were followed for a period of 1 year. Patients were classified as having SpondyloArthritis [SpA] according to several sets of criteria. Statistical analysis included logistic regression models and linear mixed model analysis. RESULTS: Of the 155 patients with joint/back pain, 13 had chronic back pain, 80 peripheral joint complaints, and 62 axial and peripheral joint complaints. Smoking, female gender, and IBD disease activity were independently associated with IBD joint/back pain. The Assessment in Spondyloarthritis International Society criteria for axial and peripheral SpA were fulfilled in 12.3% of patients, with 9.7% [n = 15] receiving a rheumatological diagnosis of arthritis. During the 12-month follow-up, the majority of the patients reporting joint/back pain remained stable. CONCLUSIONS: In our cohort, the majority of IBD patients reported joint/back pain and SpA was relatively common. To facilitate effective care, gastroenterologists should be aware of the various features of SpA to classify joint complaints and, by making use of an efficient referral algorithm, to refer CBP patients to the rheumatologist.

Synovitis and radiographic progression in non-erosive and erosive hand osteoarthritis: is erosive hand osteoarthritis a separate inflammatory phenotype?

OBJECTIVE: To compare the prevalence of synovitis, pain and radiographic progression in non-erosive and erosive hand osteoarthritis (HOA), and to explore whether the different rate of disease progression is explained by different levels of synovitis and structural damage. DESIGN: We included 31 and 34 participants with non-erosive and erosive HOA at baseline, respectively. Using Generalized Estimating Equations, we explored whether participants with erosive HOA had more synovitis (by MRI, ultrasound and clinical examination) independent of the degree of structural damage. Similarly, we explored whether pain at baseline and radiographic progression after 5 years were higher in erosive HOA, independent of the levels of synovitis and structural damage. All analyses were adjusted for age and sex. RESULTS: Power Doppler activity was found mainly in erosive HOA. Participants with erosive HOA demonstrated more moderate-to-severe synovitis, assessed by MRI (OR = 1.73, 95% CI 1.11-2.70), grey-scale ultrasound (OR = 2.02, 95% CI 1.25-3.26) and clinical examination (OR = 1.80, 95% CI 1.44-2.25). The associations became non-significant when adjusting for more structural damage. The higher frequency of joint tenderness in erosive HOA was at least partly explained more structural damage and inflammation. Radiographic progression (OR = 2.53, 95% CI 1.73-3.69) was more common in erosive HOA independent of radiographic HOA severity and synovitis (here: adjusted for grey-scale synovitis by ultrasound). CONCLUSION: Erosive HOA is characterized by higher frequency and more severe synovitis, pain and radiographic progression compared to non-erosive HOA. The higher rate of disease progression was independent of baseline synovitis and structural damage.

Effect of certolizumab pegol over 96†weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure.

OBJECTIVE: Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. METHODS: RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. RESULTS: Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. CONCLUSIONS: CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. TRIAL REGISTRATION NUMBER: NCT01087788.