Elizabeth Araujo

Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA

Objective To determine whether there is an additive effect of anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) on the number and size of bone erosions in patients with rheumatoid arthritis (RA) Methods 242 patients with RA received high-resolution peripheral quantitative CT (HR-pQCT) scans of the metacarpophalangeal joints. Demographic and disease-specific parameters including ACPA and RF levels were recorded from all patients. Erosion numbers and their size were assessed in 238 patients at 714 individual joints (MCP 2, 3 and 4) and 5712 sites (each 4 quadrants in metacarpal heads and phalangeal bases). The volume of erosions was calculated by a semiellipsoid formula. Results Of the 238 patients, 112 patients showed RF and ACPAs (ACPAs+RF+), 28 only RF (RF+), 29 only ACPAs (ACPA+) and 69 were antibody negative (NEG). Erosion number and size were highest in RF+ACPAs+ patient group with significant differences compared with NEG patients with respect to erosion number (p=0.001) and to ACPA-negative patients with respect to erosion size (p<0.001). Results maintained significance in a linear mixed model showing ACPAs+RF+ status and disease duration being associated with higher number (p=0.017 and p=0.005, respectively), and larger size (p=0.014 and p=0.013, respectively) of bone erosions. Furthermore, erosion size was influenced by the presence and titre of RF only in ACPA-positive patients with RA but not in ACPA-negative patients. Conclusions ACPAs and RF show an additive effect on erosion number and erosion size. Concomitant presence of ACPAs and RF is associated with higher erosive disease burden in patients with RA. Furthermore, RF influences erosion size only in ACPA-positive but not in ACPA-negative patients.

Tophus resolution with pegloticase: a prospective dual-energy CT study

Objective To investigate the effect of intensive lowering of serum uric acid (SUA) levels by pegloticase on the resolution of tophi in patients with refractory gout. Methods Descriptive study in patients with refractory gout receiving pegloticase treatment. SUA levels were measured before and after each infusion. Dual-energy CT (DECT) scans were taken from all patients before the first infusion and after the last infusion. Computerised tophus volumes were calculated for the baseline and follow-up assessments and compared with each other. Results 10 patients with refractory gout and baseline mean SUA level of 8.1 mg/dL were enrolled. Patients were treated for a mean of 13.3 weeks. Pegloticase effectively reduced tophi in all patients showing a decrease in volume by 71.4%. Responders, showing reduction of SUA level below 6 mg/dL during at least 80% of the treatment time, were virtually cleared from tophi (−94.8%). Dependent on their anatomical localisation, resolution of tophi showed different dynamics, with articular tophi showing fast, and tendon tophi slow, resolution. Conclusions Tophi are highly sensitive to pegloticase treatment, particularly when located at articular sites. Debulking of disease and a tophus-free state can be reached within a few months of pegloticase treatment. DECT allows for comprehensively assessing tophus burden and monitoring treatment responses.

High incidence of disease recurrence after discontinuation of disease-modifying antirheumatic drug treatment in patients with psoriatic arthritis in remission

Objective To investigate the possibility of drug-free remission in patients with psoriatic arthritis (PsA) in continuous remission. Methods Prospective observational study in disease-modifying antirheumatic drug (DMARD)-treated PsA patients in continuous disease remission (no musculoskeletal symptoms, no or minimal skin/nail disease) for at least 6 months. Demographic, disease-specific and ultrasound parameters were assessed at baseline. DMARDs (traditional or biologic) were discontinued at the initial visit, and patients were followed for a maximum of 6 months for recurrence of disease. Results 26 patients (methotrexate monotherapy: N=14; tumour necrosis factor inhibitors: N=12) with a mean age of 55.2 years, absence of musculoskeletal symptoms and minimal skin disease (mean Psoriasis Area Severity Index (PASI): 0.21) were enrolled. Incidence of recurrence of disease was high (N=20, 76.9%) and occurred rapidly (74.50±51.72 days) after treatment discontinuation. Male PsA patients were significantly more likely to lose remission. Long disease duration, more severe skin involvement and the presence of synovial hypertrophy by ultrasonographic examination at baseline decreased the likelihood for drug-free remission. Reinitiation of DMARDs promptly restored remission in all PsA patients with recurrence of disease. Conclusions This study shows that the chance to reach drug-free remission in PsA patients is low. Discontinuation of DMARD therapy cannot be recommended in patients with PsA.

The Interaction of Physical Function and Emotional Well-being in Rheumatoid Arthritis—What is the Impact on Disease Activity and Coping?

OBJECTIVE To evaluate the impact of the interaction of physical function and emotional well-being on disease-related parameters and coping with rheumatoid arthritis. METHODS A cross-sectional survey among 177 RA patients included demographic and disease-related variables as well as the following patient-reported outcome measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) (physical function), Mental Component Summary Scale of the SF-36 (MCSS) for emotional well-being, Rheumatoid Arthritis Disease Activity Index (RADAI), and Coping with Rheumatoid Arthritis Questionnaire (C-RAQ). Based on HAQ-DI and MCSS, six categories representing various levels of physical and emotional impairment were formed. Multivariate analysis of variance and a subsequent discriminant analysis were used to evaluate whether demographic and disease-related variables and coping strategies differed between these categories. RESULTS Patients with moderate to high impairment of physical function and emotional well-being reported significantly higher disease activity and a more frequent use of distancing and active problem solving coping strategies than patients with low-level impairment (p<0.001-0.043). Furthermore, these patients reported experiencing significantly higher levels of helplessness (p<0.001-0.032). Results from the discriminant analysis highlighted a combination of disease activity and helplessness to differentiate best between patients with either low or high impairment of physical function and emotional well-being (p<0.001). CONCLUSION Aside from perceived disease activity, helplessness, and distancing as well as active problem solving allowed for a good discrimination between the different levels of impairment of physical function and emotional well-being. Encouraging and educating patients on how to cognitively reframe their current situation might play a key role in reducing the level of helplessness resulting from impairments of physical function and emotional well-being.

Development of a dual energy computed tomography scoring system for measurement of urate deposition in gout

To develop a semiquantitative dual‐energy computed tomography (DECT) scoring system for measurement of urate deposition in gout.

Prevalence of monosodium urate deposits in a population of rheumatoid arthritis patients with hyperuricemia

OBJECTIVES To investigate the prevalence of monosodium urate (MSU) crystal deposits, indicative for gout, in a population of rheumatoid arthritis (RA) patients with concomitant hyperuricemia and to analyze the clinical and disease-specific characteristics of RA patients who exhibit MSU crystal deposits. METHODS Overall, 100 consecutive patients with the diagnosis of RA and a serum urate level above 6mg/dl underwent dual energy computed tomography (DECT) of both feet and hands to search for MSU crystals in a prospective study between October 2011 and July 2013. Presence and extent of MSU crystal deposits on DECT was assessed by automated volume measurement. Demographic and disease-specific characteristics were recorded and included into two logistic regression models to test for the factors associated with MSU crystal deposits in RA. RESULTS Hyperuricemic RA patients were mostly male (55%), over 60 years of age (63 ± 11 years), had established disease (8.7 ± 10.5 years) and a mean disease activity score 28 (DAS 28) of 3.2. In total, 20 out of 100 patients displayed MSU crystal deposits in DECT. Interestingly, the majority (70%) of the RA patients positive for MSU crystal deposits were seronegative RA patients. Hence, every third seronegative RA patient had MSU crystal deposits. According to logistic regression model analysis, seronegative status correlated positively with presence of urate deposits (p = 0.019). CONCLUSIONS These data show that a considerable number of RA patients display periarticular MSU crystal deposits. Seronegative patients were shown to be predominantly affected with every third patient being positive for urate deposits.

Psychometric properties of three single-item pain scales in patients with rheumatoid arthritis seen during routine clinical care: a comparative perspective on construct validity, reproducibility and internal responsiveness.

Objective To investigate the construct validity, reproducibility (ie, retest reliability) and internal responsiveness to treatment change of common single-item scales measuring overall pain in patients with rheumatoid arthritis (RA) and to investigate the corresponding effect of common pain-related comorbidities and medical consultation on these outcomes. Methods 236 patients with RA completed a set of questionnaires including a visual analogue scale (VAS), a numerical rating scale (NRS) and a verbal rating scale (VRS) measuring overall pain before and immediately after routine medical consultation as well as 1 week after the patients visit. Construct validity and retest reliability were evaluated using the Bravais-Pearson correlation while standardised response means (SRM) were calculated for evaluating internal responsiveness. Differences in the perception of pain were calculated using dependent samples t-tests. Results In the total sample, construct validity was good across all three time points (convergent validity of pain scales: rT1–T3=0.82–0.92, p<0.001; discriminant validity as correlation of pain scales with age: rage=0.01–0.16, p>0.05). In patients maintaining antirheumatic treatment, retest reliability of pain scales was confirmed for all scales and across time points (rVAS=0.82–0.95, rNRS=0.89–0.98, rVRS=0.80–0.90, p<0.001), while the internal responsiveness of scales to a change in treatment was low across all scales (SRM=0.08–0.21). The VAS especially suggested a change in pain perception after medical consultation in patients maintaining therapy. Conclusions The VAS, NRS and VRS are valid and retest reliable in an outpatient clinical practice setting. The low pain scales’ internal responsiveness to treatment change is likely to be due to the short follow-up period. Patients with RA maintaining antirheumatic therapy seem to experience less pain after medical consultation.

SAT0283 High Incidence of Flare After Discontinuation of Disease Modifying Anti-Rheumatic Drugs in Patients with Psoriatic Arthritis

Background In the era of modern anti-rheumatic therapy, it is now possible to contemplate the idea of clinical remission in patients with psoriatic arthritis (PsA)1. It is however unknown whether patients in clinical remission can stop methotrexate (MTX) or tumor necrosis factor inhibitor (TNFi) treatment2. Objectives To investigate drug-free remission in patients with PsA and potential predictors for flare. Methods Patients with PsA in remission (no musculoskeletal symptoms, no or minimal skin/nail disease) for at least 6 months were included. At baseline the following parameters were assessed: age, sex, BMI, disease duration, duration of remission, swollen joint count, tender joint count, VAS-pain, VAS-global, NAPSI, PASI, MASES, LDI, HAQ-DI, SF-36, FACIT-F, anti-rheumatic therapy (MTX, TNFi), ESR and CRP. In addition, ultrasound of 20 joints and 20 enthesis was performed. After discontinuation of therapy at day 1, patients were followed for 6 months for the occurrence of flares. Results 26 patients (20 males, 6 females) were enrolled. Mean ± SD age was 55 ± 14 years, mean ± SD disease duration was 6.1 ± 6.2 years, mean ± SD duration of remission was 23.9 ± 23.7 months. 15 patients received MTX monotherapy, 11 were treated with TNFi (6 in combination with MTX). We observed a high incidence of flares (76.9%, N= 20), with flares occurring relatively early (74.50 ± 50.79 days). There was no difference in flare rates between the MTX and TNFi groups. Due to our low number of patients, predictors of flare could not be determined but some important trends were observed. Male patients were more likely to flare (OR=18.00; [95%CI: 1.92-168.99]; p=0.011); patients with lower BMI (U=33.50, z=-1.61, p=0.107, r=0.32) and longer disease duration (U=35.50, z=-1.51, p=0.132, r=0.30) showed medium effect trends to flare. Further, presence of calcifications at the enthesial sites was associated with flares (U=33.50, z=-1.50, p=0.133, r=0.30). Conclusions This study showed a high incidence of flare in patients with PsA after discontinuing therapy. Although remission in PsA is an obtainable goal, drug-free remission may not be realistic for the majority of patients. Our study suggests that some baseline characteristics, such as male sex, low BMI, longer disease duration and enthesial calcifications predict flares of PsA after discontinuation of anti-rheumatic therapy. References Kavanaugh A., Fransen J., Defining remission in psoriatic arthritis. Clin Exp Rheumatol 2006: 24(Suppl. 43): S83-S87. Saber TP, et al., Remission in psoriatic arthritis: is it possible and how can it be predicted? Arthritis Research & Therapy 2010, 12:R94. Disclosure of Interest None Declared

Effects of ustekinumab versus tumor necrosis factor inhibition on enthesitis: Results from the enthesial clearance in psoriatic arthritis (ECLIPSA) study

OBJECTIVES To date, all studies addressing on anti-inflammatory drugs in PsA have been carried out in psoriatic arthritis (PsA) patients with polyarticular disease. Specific studies on enthesitis are missing. IL-23 is considered to play a central role in the development of enthesitis. We therefore speculated that therapeutic inhibition of IL-12/IL-23 is particularly effective in enthesitis-driven PsA patients. METHODS Enthesial CLearance In PSoriatic Arthritis (ECLIPSA) is a prospective randomized-controlled open-label study. Patients with PsA with active enthesitis were randomized 1:1 to receive either ustekinumab (UST; arm 1) or tumor necrosis factor inhibitors (TNFi; arm 2). Primary endpoint was complete clearance of enthesitis, defined by Spondyloarthritis Research Consortium of Canada (SPARCC) index equal to zero at 24 weeks. RESULTS 51 patients (UST = 25; TNFi = 26) were screened, 47 enrolled (UST = 23; TNFi = 24) and 46 completed the study. Mean ± SD SPARCC index at baseline was 4.8 ± 2.6 in the UST group and 3.5 ± 2.3 in the TNFi group with no significant difference. After 24 weeks, 73.9% of UST patients and 41.7% of TNFi patients reached the primary endpoint (SPARCC = 0) indicating clearance from enthesitis (p = 0.018). UST achieved superior responses as compared to TNFi with respect to enthesitis (p = 0.007) and psoriatic skin disease (p = 0.030) but not for arthritis (p = 0.95). CONCLUSION These results indicate that p40-IL-12/IL-23 inhibition is superior to TNFi in the clearance of enthesitis. Future stratified therapeutic approaches in PsA patients may therefore consider the presence or absence of enthesitis as a discriminator of response between different cytokine blocking modalities.

OP0217 Ustekinumab is superior to TNF inhibitor treatment in resolving enthesitis in PSA patients with active enthesitis- results from the enthesial clearance in psoriatic arthritis (ECLIPSA) study

Background IL-23 is considered to play an important role in the development of enthesitis. Ustekinumab (UST), a combined inhibitor of IL-12/IL-23 shows efficacy in psoriatic arthritis (PsA), which is driven by enthesial and synovial disease, while it has no therapeutic role in diseases driven by synovitis alone, such as rheumatoid arthritis. We therefore speculated that inhibition of IL-23 is particularly effective in enthesitis-driven PsA patients. Objectives To compare the efficacy of UST with tumor necrosis factor inhibitor (TNFi) treatment in clearing enthesitis in PsA patients. Methods ECLIPSA is a prospective randomized-controlled open study. Patients with PsA with active enthesitis were randomized 1:1, receiving either standard doses of UST (arm 1) or TNFi (arm 2). At baseline the following parameters were assessed: age, gender, BMI, disease duration, previous DMARDs, use of corticosteroids, use of NSAIDs, swollen and tender joint count, VAS-pain, VAS-global, NAPSI, PASI, MASES, SPARCC, LDI, BASDAI, BASFI, HAQ-DI, SF-36, FACIT-F, ESR and CRP. Primary endpoint was a SPARCC of 0 after 6 months. Patients were seen every 3 months and followed for a total of 6 months. In order to investigate the effects of study treatment over time we used 2x3 mixed design ANOVA models for both physicians and patients reported outcomes. Furthermore, exploratory logistic regression was used to predict a SPARCC of 0 at month 6 from baseline SPARCC, PASI, NAPSI, FACIT-F and BASDAI while additionally accounting for age, gender, PsA duration and study treatment. Results 51 patients (UST=25; TNFi=26) were screened and 47 patients (UST=23; TNFi=24) were enrolled with 4 patients not presenting signs of active enthesitis at baseline. Mean ± SD age was 59.11±12.16 years and mean ± SD disease duration was 6.4±7.79 years. Mean± SD SPARCC at baseline was 4.87±2.69 in the UST group and 3.88±2.52 in the TNFi group. Other baseline characteristics were similar between both groups with exception of HAQ-DI, BASFI and SF-36 mental scale. In regards to the effect of study treatment (TNFi vs. UST) and time, the corresponding ANOVAs suggested an important interaction of both factors for measures of enthesitis (MASES and SPARCC), patient-reported disease activity (BASDAI and BASFI), physical well-being (SF-36 physical component summary scale), and PASI all p≤0.044 with superiority of UST. However, TNFi was superior to UST with respect to improvement of fatigue (FACIT-F), p<0.001. After 6 months, 17 out of 24 UST patients (70.8%) and 10 out of 26 TNFi patients (38.4%) reached the primary endpoint (SPARCC=0). Logistic regression predicting enthesitis-free state of disease was significantly related to study treatment only, with patients receiving UST being more likely to show no signs of enthesitis at month 6 (OR=0.037; p=0.005). Conclusions These results show that UST is superior to TNFi in resolving the enthesitis component of disease in PsA patients with active enthesial disease. Based on these data more stratified treatment approaches can be designed in PsA patients, where enthesitis-driven patients are targeted by IL-23/IL-17 pathway inhibitors, while more systemic disease manifestations of PsA, such as patients with polyarticular disease or those with high-level fatigue are targeted by TNFi. Disclosure of Interest None declared