Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial.

OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA). METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26. RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)). CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA. TRIAL REGISTRATION NUMBER: NCT03058900.

A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis: results from the OPERA randomised controlled trial.

OBJECTIVES: To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis (ERA), and whether adalimumab provides an additional effect. METHODS: In a double-blind, placebo-controlled trial, 85 disease-modifying antirheumatic drug-naïve patients with ERA were randomised to receive methotrexate, intra-articular glucocorticosteroid injections and placebo/adalimumab (43/42). Contrast-enhanced MRI of the right hand was performed at months 0, 6 and 12. Synovitis, osteitis, tenosynovitis, MRI bone erosion and joint space narrowing (JSN) were scored with validated methods. Dynamic contrast-enhanced MRI (DCE-MRI) was carried out in 14 patients. RESULTS: Synovitis, osteitis and tenosynovitis scores decreased highly significantly (p<0.0001) during the 12-months' follow-up, with mean change scores of -3.7 (median -3.0), -2.2 (-1) and -5.3 (-4.0), respectively. No overall change in MRI bone erosion and JSN scores was seen, with change scores of 0.1 (0) and 0.2 (0). The tenosynovitis score at month 6 was significantly lower in the adalimumab group, 1.3 (0), than in the placebo group, 3.9 (2), Mann-Whitney: p<0.035. Furthermore, the osteitis score decreased significantly during the 12-months' follow-up in the adalimumab group, but not in the placebo group, Wilcoxon: p=0.001-0.002 and p=0.062-0.146. DCE-MRI parameters correlated closely with conventional MRI inflammatory parameters. Clinical measures decreased highly significantly during follow-up. CONCLUSIONS: A treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid in patients with ERA effectively decreased synovitis, osteitis and tenosynovitis and halted structural damage progression as judged by MRI. The findings suggest that addition of adalimumab is associated with further suppression of osteitis and tenosynovitis.

Shared care or nursing consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis outpatients with low disease activity--patient outcomes from a 2-year, randomised controlled trial.

OBJECTIVES: To compare patient outcomes of three regimes of follow-up care for rheumatoid arthritis (RA) outpatients with low disease activity. METHODS: RA outpatients (n=287) with Disease Activity Score (DAS28-CRP)<3.2 and Health Assessment Questionnaire<2.5 from two Danish rheumatology clinics were randomised to 2-year follow-up by either: (1) planned rheumatologist consultations, (2) shared care without planned consultations or (3) planned nursing consultations. The primary outcome was change in disease activity. DAS28-CRP, Health Assessment Questionnaire, visual analogue scale (VAS)-pain, fatigue, global health, confidence and satisfaction, quality-of-life by the Short Form 12 and self-efficacy measured by the RA Self-Efficacy questionnaire and the Arthritis Self-Efficacy Scale, were recorded annually and safety measures were recorded. x-Rays of hands and feet were taken at baseline and at 2-year follow-up. Mixed effect models were used to explore differences between the three groups over time. RESULTS: At 2-year follow-up, the group allocated to nursing consultations had lower disease activity than the group that underwent rheumatologist consultations (DAS28-CRP -0.3, p=0.049). The nursing group increased their self-efficacy (Arthritis Self-Efficacy Scale 18.8, p=0.001), confidence (10.7, p=0.001) and satisfaction (10.8, p<0.001) compared with the rheumatologist group. The shared care group reported a transient lower satisfaction compared with the rheumatologist group after 1 year (-8.8, p=0.004). No statistically significant differences were seen in other outcome variables. CONCLUSIONS: It is safe to implement shared care and nursing consultations as alternatives to rheumatologist consultations for RA outpatients with low disease activity without deterioration in disease control. Nursing consultations can enhance patients' self-efficacy, confidence and satisfaction.

Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial.

OBJECTIVES: An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency of low disease activity (DAS28CRP<3.2) at 12 months. METHODS: In 14 Danish hospital-based clinics, 180 disease-modifying anti-rheumatic drugs (DMARD)-naïve ERA patients (<6 months duration) received methotrexate 7.5 mg/week (increased to 20 mg/week within 2 months) plus adalimumab 40 mg every other week (adalimumab-group, n=89) or methotrexate+placebo-adalimumab (placebo-group, n=91). At all visits, triamcinolone was injected into swollen joints (max. four joints/visit). If low disease activity was not achieved, sulfasalazine 2 g/day and hydroxychloroquine 200 mg/day were added after 3 months, and open-label biologics after 6-9 months. Efficacy was assessed primarily on the proportion of patients who reached treatment target (DAS28CRP<3.2). Secondary endpoints included DAS28CRP, remission, Health Assessment Questionnaire (HAQ), EQ-5D and SF-12. Analysis was by intention-to-treat with last observation carried forward. RESULTS: Baseline characteristics were similar between groups. In the adalimumab group/placebo group the 12-month cumulative triamcinolone doses were 5.4/7.0 ml (p=0.08). Triple therapy was applied in 18/27 patients (p=0.17). At 12 months, DAS28CRP<3.2 was reached in 80%/76% (p=0.65) and DAS28CRP was 2.0 (1.7-5.2) (medians (5th/95th percentile ranges)), versus 2.6 (1.7-4.7) (p=0.009). Remission rates were: DAS28CRP<2.6: 74%/49%, Clinical Disease Activity Index≤2.8: 61%/41%, Simplified Disease Activity Index<3.3: 57%/37%, European League Against Rheumatism/American College of Rheumatology Boolean: 48%/30% (0.0008

Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial.

OBJECTIVES: The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins. METHODS: This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel). RESULTS: Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-γ (IFN-γ), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-γ, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-γ (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-γ, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6. CONCLUSIONS: Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-γ. TRIAL REGISTRATION NUMBER: NCT03058900.

The impact of an ultrasound atlas for scoring salivary glands in primary Sjögren's syndrome: a pilot study.

The objective of this pilot study was to assess the impact of a salivary gland ultrasound (SGUS) atlas for scoring parenchymal changes in Sjögren's syndrome by assessing the reliability of the scoring system (0-3), without and with the use of the SGUS atlas. Ten participants with varying experience in SGUS contributed to the reliability exercise. Thirty SGUS images of the submandibular and parotid gland with abnormalities ranging from 0 to 3 were scored using the written definitions of the OMERACT SGUS scoring system and using the SGUS atlas based on the OMERACT scoring system. For intra-reader reliability, two rounds were performed without and with the atlas-in the 2nd round the 30 images were rearranged in random order by a physician not included in the scoring. Inter-reader reliability was also determined in both rounds. Without using the atlas, the SGUS OMERACT scoring system showed fair inter-reader reliability in round 1 (mean kappa 0.36; range 0.06-0.69) and moderate intra-reader reliability (mean kappa 0.55; range 0.28-0.81). With the atlas, inter-reader reliability improved in round 1 to moderate (mean kappa 0.52; range 0.31-0.77) and intra-reader reliability to good (mean kappa 0.69; range 0.46-0.86). Higher intra-reader reliability was noted in participants with previous SGUS experience. The SGUS atlas increased both intra- and inter-reader reliability for scoring gland pathology in participants with varying SGUS experience suggesting a possible future role in clinical practice and trials. Key Points • Ultrasonography can detect parenchymal changes in salivary glands in patients with Sjögren's disease. • An ultrasound atlas may improve reliability of scoring parenchymal changes in salivary glands.

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial.

OBJECTIVE: We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT). METHODS: This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1 H Nuclear Magnetic Resonance. RESULTS: Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02). CONCLUSION: Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

The Prognostic Value of Pain Phenotyping in Relation to Treatment Outcomes in Patients with Axial Spondyloarthritis Treated in Clinical Practice: A Prospective Cohort Study.

Despite the control of inflammation, many patients with axial spondyloarthritis (axSpA) still report pain as a significant concern. Our objective was to explore the prognostic value of the painDETECT questionnaire (PDQ) in relation to treatment outcomes in axSpA patients treated in clinical practice. AxSpA patients with high disease activity initiating or switching a biological Disease-Modifying Antirheumatic Drug (bDMARD) were eligible. The PDQ score (range: -1 to 38) was used to distinguish participants with nociceptive pain (NcP) mechanisms from participants with a mixed pain mechanism (MP). The primary outcome was the proportion of individuals achieving a 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 12 weeks; logistic regression analysis models were used to determine the prognostic value of the nociceptive pain phenotype. Changes in continuous outcomes such as the Assessment of SpondyloArthritis International Society (ASAS) core outcome domains were analyzed using analysis of covariance (ANCOVA). Health-related quality of life (HR-QoL) was addressed using the Medical Outcomes Study SF-36. During a period of 22 months, 49 axSpA patients were included. Twenty (41%) had an NcP phenotype according to the PDQ score. BASDAI50 responses were reported by 40% (8/20) and 28% (8/29) NcP and MP groups, respectively. However, a prognostic value was not found in relation to the primary outcome (crude odds ratio [95% confidence interval]: 1.75 [0.52 to 5.87]). Across most of the secondary outcomes, axSpA NcP phenotype patients were reported having the most improvements in the HR-QoL measures. These data indicate the influence of personalized management strategies according to patients' pain phenotypes for stratification of axSpA patients in randomized controlled trials.

Experiences and perceptions of patients with psoriatic arthritis participating in a trial of faecal microbiota transplantation: a nested qualitative study.

OBJECTIVES: Patients' first-hand experiences of faecal microbiota transplantation (FMT) performed in a rheumatological care setting have yet to be elucidated. The objectives were to explore participants' perceptions of being part of an FMT trial thereby identifying potential trial participation effects and enlightening the patient perspective on the outlook for future FMT trials in rheumatic diseases. DESIGN: In a qualitative study nested within a double-blind, randomised, placebo-controlled trial (RCT) testing FMT as a potential new antirheumatic treatment, semistructured telephone interviews were conducted following the trial participants' final 26-week visit. Qualitative researchers, who did not take part in the main trial, performed the interviews and the primary analysis. The experiences explored related to the conduct of the RCT and changes in the participants' everyday life. The analysis was carried out using a thematic approach. SETTING: A Danish rheumatology university outpatient clinic with nationwide inclusion. PARTICIPANTS: The study included 10 patients with psoriatic arthritis (PsA) who were unaware of their treatment allocation (FMT/sham transplantation) and completed the final 26-week trial visit. RESULTS: Participation in the RCT influenced the patients' understanding of PsA and induced positive changes in their everyday life. Renewed hopes for the future in addition to a feeling of enhanced care contributed to significant trial participation effects. FMT was deemed a tolerable and safe treatment. CONCLUSIONS: Discrepancies between the clinical and the research setting should be considered when discussing the clinical relevance of the results of the RCT. Overall, patients with PsA who have participated in an RCT testing FMT find the treatment acceptable and safe encouraging more research into the field of microbiota-targeted interventions in rheumatic diseases. TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

[Osteoarthritis of facet and sacroiliac joints].

This review gives a summary of osteoarthritis (OA) of the spine involving the facet and the sacroiliac joints. Facet joint OA is widely prevalent in adults, and is thought to be a common cause of back and neck pain. The prevalence of facet and SI-joint mediated pain increases with age, suggesting that OA might have a particularly important role in older adults with spinal pain. Treatment options of symptomatic facet- and SI-joint degeneration consist of non-opioid analgesics, physiotherapy or in patients with persistent back or leg pain of either spinal decompression or fusion.

Efficacy of methotrexate in management of peripheral psoriatic arthritis - a systematic review.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory joint disease associated with psoriasis. Treatment consists of disease-modifying antirheumatic drugs with methotrexate (MTX) as first choice, yet documentation of the efficacy of this treatment is limited. The objective of this review is to make an accessible overview of the existing evidence on the clinical effect of MTX in the treatment of peripheral PsA. METHODS: A systematic search for randomised controlled trials was conducted using the PubMed, Embase and Cochrane Library databases. Studies examining the effect of MTX on peripheral arthritis in adult patients with PsA were included. Only trials published in English were considered and for each study, the methodological quality was assessed. RESULTS: Seven studies qualified given the selected criteria. None of the two placebo-controlled trials included found a significant reduction in tender and swollen joint counts. Trials comparing MTX to combination therapy with TNF-alpha inhibitor or ciclosporin A demonstrated some clinical benefits of MTX; however, combination therapy was superior to MTX monotherapy. In a strategy trial, patients were able to reach minimal disease activity with MTX treatment alone, pointing towards some efficacy of MTX on clinical manifestations. CONCLUSIONS: Clinical benefits have been found in the treatment of PsA with MTX. MTX has demonstrated clinical efficacy in the treatment of psoriasis; however, the treatment of peripheral arthritis still lacks supportive evidence. More controlled trials need to be conducted to underpin evidence-based use of MTX.

The impact of sex and disease classification on patient-reported outcome measures in axial spondyloarthritis: a descriptive prospective cross-sectional study.

BACKGROUND: The aim of this study was to explore the impact of sex and disease classification on outcomes in axial spondyloarthritis (axSpA) patients, including both radiographic (r-) axSpA and non-radiographic (nr-) axSpA, in males and females, respectively. METHODS: AxSpA patients were consecutively recruited from two rheumatology outpatient university clinics. We explored how sex and axSpA disease classification affected patient-reported outcome measures (PROMs). General linear models were used to investigate if there was an association between the continuous variables and each of the main effects of interest (sex and axSpA classification), as well as the possible interaction between them. Categorical outcome measures were analyzed with the use of logistic regression with the same fixed effects. We analyzed the relationship between tender point count (TPC) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The prevalence of extra-articular manifestations (EAMs) and the Charlson Comorbidity Index (CCI) were determined. RESULTS: According to the protocol, a total of 100 outpatients with axSpA were enrolled (r-axSpA males 30, r-axSpA females 10, nr-axSpA males 25, nr-axSpA females 35). The BASDAI scores appeared higher among nr-axSpA females (median [Q1; Q3], 47 [21; 60]) compared with the combined median for the 3 other subgroups 25 [12; 25]. Female sex was associated with a higher number of tender point count (TPC, P < 0.001). TPC and BASDAI were correlated for female nr-axSpA patients (r = 0.44, P = 0.008) and male nr-axSpA patients (r = 0.56, P = 0.003). Being classified as nr-axSpA was associated with a lower SF-36 Mental Component Summary (median for the 4 subgroups: nr-axSpa females 46.7, nr-axSpA males 52.3 vs. r-axSpA males 56.9 and r-axSpA females 50.4). EAMs were frequent (up to 50%). The CCI was low in all 4 subgroups, and no difference in the CCI between the subgroups was observed (P = 0.14). However, male sex had a significant impact on the CCI (P = 0.03). CONCLUSIONS: In summary, patients with r-axSpA, regardless of sex, appeared less affected on most PROMs compared with nr-axSpA patients. However, female sex was associated with a higher number of TPC. TPC could possibly confound disease activity outcomes such as BASDAI, and one can consider different thresholds for defining high disease activity depending on the patient's sex. TRIAL REGISTRATION: The trial is registered and approved by the Region of Southern Denmark's Ethics Committee ( S-20150219 ). Registered 19 February 2015.

Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial.

INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA. METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study. ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s). TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

Clinical characteristics of importance to outcome in patients with axial spondyloarthritis: protocol for a prospective descriptive and exploratory cohort study.

INTRODUCTION: Spondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints or predominantly peripheral arthritis. The two main entities of axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr-axSpA). Tumour necrosis factor-α inhibitors have revolutionised the treatment of patients with axSpA who failed to respond to non-steroidal anti-inflammatory drugs and physical therapy. Chronic pain is common in patients with SpA and may still persist despite the lack of signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool developed to detect neuropathic pain components. The primary objective is to explore the prognostic value of the PDQ regarding treatment response in patients with axSpA 3 months after initiating a biological agent. Secondary aim is to evaluate the impact of extra-articular manifestations, comorbidities and patient-reported outcomes and elucidate if these factors influence treatment response. METHOD AND ANALYSIS: We will include 60 participants (≥18 years of age) diagnosed with axSpA independent of main entity, who initiate or switch treatment of a biologic. Data will be collected at baseline and at endpoint following Danish clinical practice (≥3 months) of treatment with biologics. We will explore whether the PDQ and other phenotypical patient characteristics are prognostically important for response to biological therapy according to established response criteria like 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease Activity Score. ETHICS AND DISSEMINATION: The study is approved by the Region of Southern Denmark's Ethics committee (S-20160094) and has been designed in cooperation with patient representatives. The study is registered at clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through publication(s) in international peer-reviewed journal(s).

Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab-a substudy of the optimized treatment algorithm in early RA (OPERA) trial.

This study aims to investigate 1-year hand bone loss (HBL1-year) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strategy +/- adalimumab and to determine if HBL6months is associated with radiographic progression after 2 years. In a clinical trial (OPERA) of 180 treatment-naive early RA patients, bone mineral density (BMD) was estimated from hand radiographs with digital X-ray radiogrammetry (DXR) at baseline, after 6 (n = 90) and 12 months (n = 70) of follow-up. Baseline and 2-year radiographs were scored according to the Sharp/van der Heijde method. Baseline characteristics and HBL6months (0-6 months changes in DXR-BMD) were investigated as predictors of structural damage by univariate linear (∆ total Sharp/van der Heijde score (TSS) as dependent variable) and logistic (+/-radiographic progression (∆TSS >0) as dependent variable) regression analyses. Variables with p < 0.10 were included in multivariable models. In 70 patients with available HBL1-year data, HBL1-year was median (interquartile range (IQR)) -1.9 (-3.3; -0.26 mg/cm2) in the MTX + placebo group and -1.8 (-3.6; 0.06) mg/cm2 in the MTX + adalimumab group, p = 0.98, Wilcoxon signed-rank. Increased HBL (compared to general population reference values) was found in 26/37 and 23/33 patients in the MTX + placebo and MTX + adalimumab groups, chi-squared = 0.99. In 90 patients with HBL6months data and 2-year radiographic data, HBL6months was independently associated with ∆TSS after 2 years (ß = -0.086 (95% confidence interval = -0.15; -0.025) TSS unit/mg/cm2 increase, p = 0.006) but not with presence of radiographic progression (∆TSS >0) (OR 0.96 (0.92-1.0), p = 0.10). In early RA patients treated with a methotrexate-based treat-to-target strategy, the majority of patients had increased HBL1-year, irrespective of adalimumab; HBL6months was independently associated with ∆TSS after 2 years.

[Paraneoplastic myasthenia gravis and polymyositis secondary to a thymoma in a young woman].

We present the case of a 33-year-old woman who within weeks developed severe swallowing difficulties and weakness in her limbs to an extent requiring hospitalization. Workup confirmed clinically suspected diagnoses of polymyositis and autoimmune myasthenia. A suspicion of malignant thymoma based on chest computed tomography was histologically verified. Patient treatment and response are presented. The case emphasizes the importance of recognizing that thymomas, in rare instances, may present with a combination of neuromuscular disorders in the same patient.