Relationship Between Fatigue and Inflammation, Disease Duration, and Chronic Pain in Psoriatic Arthritis: An Observational DANBIO Registry Study.

OBJECTIVE: Fatigue is one of the most significant symptoms, and an outcome of great importance, in patients with psoriatic arthritis (PsA), but associations between underlying components of fatigue experienced by patients in relation to the disease have been sparsely investigated. The objectives were to describe the degree of fatigue in patients with PsA, and to examine important components associated with fatigue. METHODS: We performed a cross-sectional survey including patients registered in the Danish nationwide registry DANBIO from December 2013 to June 2014. Principal component analysis (PCA) was used to identify factors associated with fatigue. RESULTS: A total of 1062 patients with PsA were included in the study. A PCA reduced co-variables into 3 components explaining 63% of fatigue in patients. The first component, contributing to 31% of fatigue, was composed of inflammatory factors including swollen and tender joints, physician's global assessment, elevated C-reactive protein (CRP), and high Pain Detect Questionnaire (PDQ) score. The second component, contributing to 17% of fatigue, consisted of increasing age and long disease duration. The third component, contributing to 15% of fatigue, consisted of high PDQ score, tender joint count, increasing age, and concomitant low CRP, suggestive of a chronic pain component consisting of central pain sensitization or structural joint damage. CONCLUSION: Fatigue in patients with PsA may be driven by clinical inflammatory factors, disease duration, and chronic pain in the absence of inflammation.

Hand exercise for women with rheumatoid arthritis and decreased hand function: an exploratory randomized controlled trial.

BACKGROUND: People with hand-related rheumatoid arthritis (RA) experience problems performing activities of daily living (ADL). Compensatory strategies to improve ADL ability have shown effective. Similarly, hand exercise has shown effect on pain, grip strength, and self-reported ability. A combination has shown positive effects based on self-report, but self-report and observation provide distinct information about ADL. The purpose of this study was to examine whether hand exercise as add on to compensatory intervention (CIP) will improve observed ADL ability in RA. METHODS: Women (n = 55) with hand-related RA were randomized to CIPEXERCISE (intervention) or CIP only (control). CIP is focused on joint protection, assistive devices, and alternative ways of performing AD. The hand-exercise program addressed range of motion and muscle strength. Primary outcome was change in observed ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Baseline measures were repeated after 8 weeks. RESULTS: Improvements in ADL motor ability in CIPEXERCISE (mean change = 0.24 logits; 95% CI = 0.09 to 0.39) and CIPCONTROL (mean change =0.20 logits; 95% CI = 0.05 to 0.35) were statistically significant, with no differences between groups (mean difference = 0.04 logits; 95% CI = - 0.16 to 0.25). Thirteen (46.4%) participants in the CIPEXERCISE and 12 (44.4%) in the CIPCONTROL obtained clinically relevant improvements (≥ 0.30 logits) in ADL motor ability; this group difference was not significant (z = 0.15; p = 0.88). CONCLUSION: Adding hand exercise to a compensatory intervention did not yield additional benefits in women with hand-related RA. The study was approved by the ethics committee 14th of April 2014 (H-3-2014-025) and registered at ClinicalTrials.gov 16th of May 2014 (NCT02140866).

The course of pain hypersensitivity according to painDETECT in patients with rheumatoid arthritis initiating treatment: results from the prospective FRAME-cohort study.

BACKGROUND: Evidence is emerging that pain in rheumatoid arthritis (RA) exists without underlying inflammation. Our objective was to evaluate the prognostic value of pain classification at treatment initiation using the painDETECT questionnaire (PDQ). Outcomes were change in DAS28-CRP and RAMRIS synovitis score. METHODS: RA patients initiating a disease-modifying anti-rheumatic drug (DMARD) or initiating/ switching a biological agent were included. Follow-up time was 4 months. Clinical examination, imaging (MRI, dynamic contrast-enhanced MRI (DCE-MRI)), and patient-reported outcomes were undertaken. The PDQ was used to differentiate pain mechanisms. Mean change (95% CI) was calculated using ANCOVA. Multivariable regression models were used to determine a prognostic value. RESULTS: A total of 102 patients were included; 75 were enrolled for MRI. Mean changes in baseline variables were greatest in the high PDQ classification group (> 18), while limited in the intermediate group (13-18). The 12 patients with high baseline PDQ score all changed pain classification group. No prognostic value of PDQ pain classification was found in relation to change of DAS28-CRP, RAMRIS score, or VAS pain. In the unadjusted model, RAMRIS score at baseline was associated with change in DAS28-CRP. The exploratory variables of DCE-MRI did not differ from other inflammatory variables. CONCLUSIONS: In RA patients a high PDQ score (non-nociceptive pain) at baseline was not associated with worse outcomes, in fact these patients had numerically greater improvement in DAS28-CRP. However, pain classification by PDQ was not independently associated with change in DAS28-CRP, RAMRIS score, or VAS pain in the prognostic models. Furthermore, patients classified with a high baseline PDQ score changed pain classification group. Patients with unclear pain mechanism had reduced numerically treatment response. TRIAL REGISTRATION: The study was approved by the Regional Ethics Committee of the Capital of Denmark April 18 2013; identification number H-3-2013-049 .

Psychometric properties of the painDETECT questionnaire in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: Rasch analysis and test-retest reliability.

BACKGROUND: Pain is inherent in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA) and traditionally considered to be of nociceptive origin. Emerging data suggest a potential role of augmented central pain mechanisms in subsets of patients, thus, valid instruments that can identify underlying pain mechanisms are needed. The painDETECT questionnaire (PDQ) was originally designed to differentiate between pain phenotypes. The objectives were to evaluate the psychometric properties of the PDQ in patients with inflammatory arthritis by applying Rasch analysis and to explore the reliability of pain classification by test-retest. METHODS: For the Rasch analysis 900 questionnaires from patients with RA, PsA and SpA (300 per diagnosis) were extracted from 'the DANBIO painDETECT study'. The analysis was directed at the seven items assessing somatosensory symptoms and included: 1) the performance of the six-category Likert scale; 2) whether a unidimensional construct was defined; 3) the reliability and precision of estimates. Another group of 30 patients diagnosed with RA, PsA or SpA participated in a test-retest study. Intraclass Correlation Coefficients (ICC) and classification consistency were calculated. RESULTS: The Rasch analysis revealed: (1) Acceptable psychometric rating scale properties; the frequency distribution peaked in category 0 except for item 5, threshold calibration >10 observations per category, no disorder in the category measures for all items, scale category outfit Mnsq <2.0, small distances (<1.4 logits) between thresholds for category 1, 2 and 3 for all items. (2) The principal component analysis supported unidimensionality; the standardized residuals showed that 53.7% of total variance was explained by the measure and the magnitude of first contrast had an eigenvalue of 1.5, no misfitting items, clinical insignificant different item hierarchies across diagnoses (DIF < 0.5 logits). (3) A targeted item-person map, person and item separation indices of 1.88(reliability = 0.78), and 13.04 (reliability = 0.99). The test-retest revealed: ICC: RA 0.86(0.56-0.96), PsA 0.96(0.74-0.99), SpA 0.93(0.76-98), overall 0.94(0.84-0.98). Classification consistency was: RA 70%, PsA 80%, SpA 90%, overall 80%. CONCLUSION: The results support that the PDQ can be used as a classification instrument and assist identification of underlying pain-mechanisms in patients suffering from inflammatory arthritis.

Ultrasound Doppler but not temporal summation of pain predicts DAS28 response in rheumatoid arthritis: a prospective cohort study.

OBJECTIVE: Previous studies have suggested a link between inflammation and central sensitization of pain in patients with RA. We conducted a prospective cohort study to determine whether US Doppler (USD), temporal summation (TS) of pain-assessed at baseline-and the potential interaction between them could predict the treatment response in RA. METHODS: Patients were recruited from Departments of Rheumatology in the Copenhagen area and from private clinics. RA patients, who were scheduled to initiate therapy with either a conventional synthetic DMARD (csDMARD; including DMARD-naïve patients) or a biologic DMARD (bDMARD) agent (including bDMARD switch), were included and examined before the start of treatment and after 4 months. During the 4 months, patients received routine care from their treating rheumatologist. RESULTS: Multiple regression analysis was conducted, with change in DAS28 as the dependent variable. In unadjusted models, baseline USD score was significantly associated with DAS28 (ß = 0.06; 95% CI: 0.02, 0.09; P < 0.001), whereas TS and their interaction were not. After adjusting for age, sex, disease duration, baseline DAS28 and whether patients initiated a csDMARD or a bDMARD, the USD score was still significantly associated with change in DAS28 (ß = 0.032; 95% CI: 0.001, 0.064; P = 0.046), whereas TS remained insignificant. CONCLUSION: USD assessed at baseline is valuable as a prognostic factor for change in disease activity in 'real-life' RA patients. We did not find evidence to suggest that TS or the interaction between USD and TS was prognostically important for this group of patients.

Can the painDETECT Questionnaire score and MRI help predict treatment outcome in rheumatoid arthritis: protocol for the Frederiksberg hospital's Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study.

INTRODUCTION: Pain in rheumatoid arthritis (RA) is traditionally considered to be of inflammatory origin. Despite better control of inflammation, some patients still report pain as a significant concern, even when being in clinical remission. This suggests that RA may prompt central sensitisation-one aspect of chronic pain. In contrast, other patients report good treatment response, although imaging shows signs of inflammation, which could indicate a possible enhancement of descending pain inhibitory mechanisms. When assessing disease activity in patients with central sensitisation, the commonly used disease activity scores (eg, DAS28-CRP (C reactive protein)) will yield constant high total scores due to high tender joint count and global health assessments, whereas MRI provides an isolated estimate of inflammation. The objective of this study is, in patients with RA initiating anti-inflammatory treatment, to explore the prognostic value of a screening questionnaire for central sensitisation, hand inflammation assessed by conventional MRI, and the interaction between them regarding treatment outcome evaluated by clinical status (DAS28-CRP). For the purpose of further exploratory analyses, dynamic contrast-enhanced MRI (DCE-MRI) is performed. METHOD AND ANALYSIS: The painDETECT Questionnaire (PDQ), originally developed to screen for a neuropathic pain component, is applied to indicate the presence of central sensitisation. Adults diagnosed with RA are included when either (A) initiating disease-modifying antirheumatic drug treatment, or (B) initiating or switching to biological therapy. We anticipate that 100 patients will be enrolled, tested and reassessed after 4 months of treatment. DATA COLLECTION INCLUDES: Clinical data, conventional MRI, DCE-MRI, blood samples and patient-reported outcomes. ETHICS AND DISSEMINATION: This study aims at supporting rheumatologists to define strategies to reach optimal treatment outcomes in patients with RA based on chronic pain prognostics. The study has been approved by The Capital region of Denmark's Ethics Committee; identification number H-3-2013-049. The results will be published in international peer-reviewed journals.

Temporal summation of pain and ultrasound Doppler activity as predictors of treatment response in patients with rheumatoid arthritis: protocol for the Frederiksberg hospitals Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study.

INTRODUCTION: Chronic pain is common in rheumatoid arthritis (RA) and may still persist despite regression of objective signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in RA. Application of the disease activity score DAS28 can classify some patients with active RA solely based on a high tender joint count and poor patient global health score. In such cases, intensified treatment with anti-inflammatory drugs would be expected to yield poorer results than in cases with DAS28 elevation due to a high score for swollen joints and C reactive protein (CRP). Evaluation of central pain sensitisation in patients with few inflammatory indices may be a predictive tool regarding the effect of anti-inflammatory treatment. Computerised pneumatic cuff pressure algometry (CPA) is a method for assessing temporal summation (ie, degree of central sensitisation). The main objective of this study was to examine the prognostic values of pressure pain-induced temporal summation, ultrasound Doppler activity and the interaction between them in relation to treatment response (DAS28-CRP change) in patients with RA initiating any anti-inflammatory therapy. METHOD AND ANALYSIS: 120 participants ≥18 years of age will be recruited. Furthermore, they must be either (1) diagnosed with RA, untreated with disease-modifying antirheumatic drugs for at least 6 months and about to initiate disease-modifying antirheumatic drug treatment or (2) about to begin or switch treatment with any biological drug for their RA. Data (clinical, imaging, blood samples, patient reported outcomes and CPA measurements) will be collected from each participant at baseline and after 4 months of anti-inflammatory treatment. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee for the Copenhagen region (H-4-2013-007). Dissemination will occur through presentations and publication in international peer-reviewed journals.

Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor α therapy: results from the nationwide Danish DANBIO registry.

OBJECTIVE: To investigate disease activity, treatment response, and drug survival, and predictors thereof, among Danish patients with psoriatic arthritis (PsA) receiving their first treatment series with a tumor necrosis factor α (TNFα) inhibitor. METHODS: Patients with PsA were identified from a prospective nationwide rheumatologic database, the Danish biologics registry DANBIO, using data registered from 2000-2009. Information was obtained on the patients' clinical response to anti-TNFα treatment (defined as achievement of the American College of Rheumatology 20% [ACR20], ACR50, and ACR70 improvement criteria or a European League Against Rheumatism [EULAR] good response at least once during the first 6 months of treatment) and duration and rate of drug adherence (referred to as drug survival), as well as predictors thereof. RESULTS: Of 764 patients with PsA, 320 received adalimumab, 260 infliximab, and 184 etanercept. Median drug survival was 2.9 years, and 1-year and 2-year drug survival rates were 70% and 57%, respectively. Clinical parameters that showed improvement over 6 months were the C-reactive protein (CRP) level, Health Assessment Questionnaire score, and 28-joint Disease Activity Score. Male sex, CRP level >10 mg/liter, concomitant methotrexate use, and low patient health visual analog scale score at baseline were associated with longer drug survival. Improvement was achieved by 59%, 45%, 24%, and 54% of patients according to the ACR20, ACR50, ACR70 response criteria and EULAR good response, respectively. A CRP level >10 mg/liter was predictive of the improvement responses (odds ratio [OR] 2.6 for ACR20, OR 3.0 for ACR50, OR 3.6 for ACR70, and OR 2.2 for EULAR good response). CONCLUSION: In these patients with PsA treated with their first TNFα inhibitor in clinical practice, high drug adherence and responder rates were observed. Moreover, increased levels of CRP at baseline were associated with both good treatment responses and continued treatment, which may be of clinical value in selecting the patients most likely to benefit from treatment with TNFα inhibitors.