Polyarticular Psoriatic Arthritis Research Articles

Comparación entre artritis reumatoide seronegativa y artritis psoriásica poliarticular: estudio transversal en una cohorte brasileña

Objectives: compare cardiovascular risk, quality of life, depression and functionality between patients with seronegative rheumatoid arthritis (RA) and polyarticular psoriatic arthritis (PsA). Materials and methods: data from 45 patients with seronegative RA and 36 with polyarticular PsA were analyzed. Questionnaires were used for depression (CES-D), functionality (Health Assessment Questionnaire, HAQ) and quality of life (SF-12). Carotid intima-media thickness (cIMT) was measured to assess cardiovascular risk. Results: the frequencies of hypertension, diabetes and dyslipidemia were similar between both groups. Patients with PsA had higher body mass index (BMI) and abdominal circumference. cIMT was equivalent between groups. Depression and quality of life did not show significant differences. Patients with RA presented worse functionality according to the HAQ. Conclusions: in our series, patients with RA and seronegative PsA had similarities in quality of life, depression and cardiovascular risk, except for differences in BMI and abdominal circumference, which were higher in PsA. Functionality was worse in AR compared to APs.

Tofaticinib as a potential therapeutic agent: a review

Tofacitinib is a Food and Drug Administration (FDA) approved second generation immunosuppressive disease-modifying anti-rheumatic drug (DMARD) that is used in the treatment of conditions like rheumatoid arthritis, ulcerative colitis polyarticular course juvenile idiopathic arthritis and psoriatic arthritis. Tofacitinib can be used to treat adult RA patients who are intolerant to methotrexate. At cellular level tofacitinib selectively inhibits Janus kinase (JAKs) in human genome and thereby stops the cytokine receptor-based signalling of interleukins viz., IL2, IL4, IL6, IL7, IL15, IL21, interferon alpha (IFNa) and IFNc in synovial fibroblasts and CD14 monocytes, thereby leading to disruption of immune and inflammatory responses. Tofacitinib is marketed as orally administered conventional tablets (5 mg and 10 mg doses) extended-release tablets (11 mg dose) and oral solutions (1 mg/ml dose). Tofacitinib is quickly absorbed after oral administration with systemic bioavailability of 74%. Tofacitinib is metabolized majorly by CYP3A4 and clearance is 70% via hepatic metabolism and 30% via renal excretion. Half-life of orally administered tofacitinib was observed to be 3 hours. Patients receiving tofacitinib therapy should be monitored for TB, renal impairment, hepatic impairment or any kind of bacterial, viral or fungal infections before initiating or during therapy. Most common reported adverse events of tofacitinib are headache, diarrhoea, nasopharyngitis, sore throat, hypertension and respiratory tract infections. Tofacitinib therapy should be cautiously used in females of reproductive age and in patients receiving renal transplant. Tofacitinib is not recommended with other immunosuppressants and vaccines. Thus, tofacitinib being a potential therapeutic agent the current review elaborates the history, detailed pharmacology, dosing, adverse events, interactions and contraindications of tofacitinib.

Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial

BackgroundEtanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial.Methods92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week.Results32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4–10), median 10 months (7–16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6–9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group.ConclusionsEscalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety.Trial registrationDutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585.

Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice.

Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study. This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA). A total of 296 patients with baseline data and 192 with completed week24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week24 (95%CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified. The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice. ClinicalTrials.gov identifier, NCT04758117.

Golimumab for Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis: Pharmacologic and Clinical Considerations.

Psoriatic arthritis is a chronic debilitating autoimmune condition, and when diagnosed in patients before the age of eighteen, it is considered pediatric polyarticular juvenile idiopathic arthritis. Monoarticular or polyarticular psoriatic arthritis can be distinguished from other arthropathies by its unique cutaneous manifestations. With numerous treatments already in clinical practice, there are numerous options for treatment. The current literature indicates an elevated level of tumor necrosis factor is present in the epidermis of patients with psoriatic arthritis when compared with the general population. For this reason, anti-tumor necrosis factor therapies have become a hallmark option for psoriatic arthritis patients. Golimumab, a human monoclonal antibody tumor necrosis factor-alpha (TNF-a) receptor antagonist, was chosen as the focus therapy for this investigation. The mechanism of action behind anti-tumor necrosis factor-alpha blockers involves the binding of human TNF-a soluble and transmembrane proteins to competitively inhibit TNF-a from binding to its cellular receptors. The present investigation evaluated current treatment options available for both juvenile- and adult-onset psoriatic arthritis and compared them with the efficacy seen with golimumab use. Pediatric patients included children ages 2-17, while adult populations included adults 18-83 years old. The Food and Drug Administration has approved golimumab for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular juvenile idiopathic arthritis. The results of four different studies reporting on the therapeutic effects and adverse events of golimumab use in psoriatic arthritis, juvenile psoriatic arthritis, juvenile idiopathic arthritis, and juvenile polyarticular arthritis were used for comparison. The meta-analysis referenced studies including children ages 2-17 with no reference mentioning children less than age 2. Based on the results of each study, it can be concluded that golimumab, a human monoclonal antibody that prevents the activation of cellular inflammatory reactions when it binds to the TNF-a receptor, is an effective option for patients with active psoriatic arthritis and psoriatic juvenile idiopathic arthritis and for patients who are no longer responding to their current treatment with adalimumab. Each study also reported minimal adverse events associated with golimumab use, and the drug can be safely used in the pediatric population.

Oral or Parenteral Methotrexate for the Treatment of Polyarticular Juvenile Idiopathic Arthritis.

Subcutaneous methotrexate injections are considered to be more effective or work faster than oral methotrexate. Therefore, the extent and the kinetics of response were analyzed in juvenile idiopathic arthritis patients treated with oral versus subcutaneous methotrexate. The BIKER databank was searched for biologics-naive juvenile idiopathic arthritis patients treated with methotrexate as initial treatment. The Juvenile Arthritis Disease Activity Score-10 defini- tion of remission and the pediatric American College of Rheumatology's response parameters were utilized as outcome criteria. A total of 410 polyarticular juvenile idiopathic arthritis patients receiving oral methotrexate were compared to 384 patients receiving subcutaneous methotrexate. Rheumatoid factor-negative polyarthritis was the most common juvenile idiopathic arthritis category (50%/51%) in this cohort followed by extended oligoarthritis (27%/26%), polyarticular psoriatic arthritis (18%/16%), and few had rheumatoid factor-positive polyarthritis (5%/8%). The oral cohort's disease duration (2.3 ± 3.0 vs. 1.9 ± 2.7) was significantly longer (P=.04), although their age at onset and baseline were similar. Furthermore, at baseline, disease activity (Juvenile Arthritis Disease Activity Score-10 16.5 ± 7.2 vs. 14.7 ± 8.2; P = .001 due to a higher active joint count 9.0 ± 10.1 vs. 7.4 ± 7.7; P = .011) was higher in the subcutaneous cohort. The weekly methotrexate doses were comparable with 13.6 ± 5.4 mg/m2 and 13.3 ± 4.5 mg/m2, respectively. With oral/subcutaneous methotrexate, a pediatric American College of Rheumatology's 90 was achieved in 98(38.3%)/128(40.4%), while 96(38.1 %)/75(40.1%) attained Juvenile Arthritis Disease Activity Score remission after 12 months of therapy. There was no difference in the early kinetics of response according to Kaplan-Meyer analysis. Adverse events including nausea, vomiting, and increased transaminases were considerably more common after methotrexate subcutaneous administration than after oral treatment. In terms of effectiveness, but not safety, our retrospective analysis found some advan- tages of subcutaneous methotrexate. Adverse effects limit treatment continuance and thus must be considered a disadvantage. Furthermore, oral methotrexate eliminates the need for injections, which is especially essential for younger children. Controlled, randomized prospective trials in children and juvenile patients are necessary for definitive recommendations for the subcutaneous route of admin- istration of methotrexate therapy.

Juvenile idiopathic arthritis of the knee: is contrast needed to score disease activity when using an augmented MRI protocol comprising PD-weighted sequences?

ObjectiveTo compare unenhanced versus enhanced knee joint magnetic resonance imaging (MRI) to assess disease activity of juvenile idiopathic arthritis (JIA).MethodsFifty-three knee joint MRI examinations were performed on a 3-Tesla system in 27 patients (age: 11.40 ± 3.61 years; 21 females, 6 males). MRI protocols comprised PD-weighted sequences in addition to the widely used standard protocol. JIA subgroups comprised oligoarticular arthritis (n = 16), extended oligoarthritis (n = 6), rheumatoid factor-negative polyarticular arthritis (n = 3), enthesitis-related arthritis (n = 1), and psoriatic arthritis (n = 1). MR images were retrospectively analyzed by 3 experienced radiologists in two readings, using JAMRIS (juvenile arthritis MRI scoring) system and a modified IPSG (international prophylaxis study group) classification. In the first reading session, only unenhanced MR images were evaluated. In a second reading session, all images before and after contrast medium application were included. In order to avoid bias, an interval of at least 2 weeks was set between the two readings. The clinical JADAS10 (juvenile arthritis disease activity score) was calculated including clinical assessment and laboratory workup and correlated with MRI scores. Statistical analysis comprised Pearson’s correlation for correlating two scoring results of unenhanced and the enhanced MRI, intra-class correlation coefficient (ICC) for inter- and intra-reader agreement. Diagnostic accuracy was calculated using ROC (receiver operating characteristics) curve analysis.ResultsInter-reader agreement determined by ICC for unenhanced and enhanced MRI scores for IPSG was moderate (0.65, 95% CI 0.51–0.76, and 0.62, 95% CI 0.48–0.75) and high for JAMRIS (0.83, 95% CI 0.75–0.89, and 0.82, 95% CI 0.74–0.89). Intra-reader agreement was good to very good for JAMRIS (0.85 95% CI 0.81–0.88, 0.87 95% CI 0.83–0.89 and 0.96 95% CI 0.92–0.98) and IPSG (0.76 95% CI 0.62–0.86, 0.86 95% CI 0.77–0.92 and 0.92 95% CI 0.86–0.96). Scores of unenhanced MRI correlated with contrast-enhanced MRI: JAMRIS (r = 0.97, R2 = 0.93, p < 0.01), modified IPSG (r = 0.95, R2 = 0.91, p < 0.01). When using JADAS10 as a reference standard, moderate accuracy for both unenhanced and enhanced MRI scores was noted: JAMRIS (AUC = 0.68, 95% CI 0.51–0.85, and AUC = 0.66, 95% 0.49–0.82), IPSG score (AUC = 0.68, 95% 0.50–0.86, and AUC = 0.61, 95% 0.41–0.81).ConclusionsOur results suggest that contrast agent application could be omitted in JIA patients with an augmented knee MRI protocol comprising PD-weighted sequence.Key Points• Unenhanced MRI can detect disease activity of the knee joint in patients with JIA with equally high accuracy compared to contrast-enhanced MRI.• The intra- and inter-reader agreement was high for unenhanced and enhanced MRI JAMRIS scores, which indicate relatively good applicability of the scoring system, even for less experienced readers.• When using the clinical JADAS10 as a reference standard for the detection of disease activity, moderate accuracy for both unenhanced and enhanced MRI scores, both JAMRIS and IPSG, was noted, which might be caused by the fact that the majority of patients had either no or minimal clinical disease activity.

10 Impact of the month of birth on the development of juvenile idiopathic arthritis among Tunisian children

BackgroundJuvenile idiopathic arthritis (JIA) is the most common inflammatory disease influenced by genetic as well as environmental factors. Prior studies from Israel and USA suggested that JIA had a seasonality of birth, with birth peaking in winter and especially in January.ObjectivesThe aim of the study was to evaluate the impact of month of birth and season, and the onset of JIA in Tunisian children.MethodsWe conducted a case-control study including 27 children with JIA compared with a homogeneous control group of 27 children hospitalized in a pediatric orthopedic unit for traumatic reasons and healthy for any chronic inflammatory rheumatism. Statistical differences between groups were also analyzed by non-parametrical tests.ResultsFifty-four patients (25 females and 29 males) were enrolled. The mean age was 11.04 ± 5.58 years and the mean duration of the diseases was 5.29 ± 3,18 years. The frequency of each JIA subset was at follows: polyarticular rheumatoid factor positive (n = 2), polyarticular rheumatoid factor negative (n = 5), psoriatic arthritis (n = 1), enthesitis-related arthritis (n = 11) and oligoarthritis (n = 8). Although the majority of children with JIA were born in November (22.2%) and December (18.5%), there was no significant difference in month of birth distribution between the cases and the controls. Likewise, there was no significant correlation between season of birth and the onset of the disease (p = 0,6).ConclusionThis study didn’t show any correlation between season and month birth, and the onset of JIA. Our result may be explained by the weather in Tunisia which is relatively warm with little variation in temperature between seasons compared with the country where they found a significant correlation. It also may be due to the limited number of our cases.

Intravenous Golimumab in Patients with Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis and Subcutaneous Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Extrapolation of Data from Studies in Adults and Adjacent Pediatric Populations.

ObjectivesTo describe the extrapolation approaches used to support intravenous (IV) golimumab for polyarticular juvenile idiopathic arthritis (pJIA) and juvenile psoriatic arthritis (jPsA) and subcutaneous (SC) ustekinumab for jPsA.MethodsPharmacokinetic, clinical response, and safety data from trials of IV golimumab and SC ustekinumab in polyarticular-course JIA (pc-JIA) (GO-VIVA) or pediatric psoriasis (PsO) (CADMUS and CADMUS Jr) and data from pivotal, phase 3 trials of these agents in adults with similar diseases were used to support extrapolation in pJIA and jPsA. In the phase 3 GO-VIVA trial, patients with pc-JIA aged 2 to < 18 years received IV golimumab 80 mg/m2 at weeks 0, 4, then every 8 weeks (Q8W). In the phase 3, randomized, placebo-controlled CADMUS trial, patients with PsO aged ≥ 12 to < 18 years received ustekinumab at weeks 0, 4, then Q12W. In the phase 3 CADMUS Jr trial, patients with PsO aged ≥ 6 to < 12 years received ustekinumab at weeks 0, 4, then Q12W. The ustekinumab analyses used data only from patients who received the standard ustekinumab dosing regimen (≤ 60 kg: 0.75 mg/kg; > 60 to ≤ 100 kg: 45 mg; > 100 kg: 90 mg).ResultsIn the 127 patients with pc-JIA treated with IV golimumab (GO-VIVA), pharmacokinetic and exposure-response results were similar to those in adults with rheumatoid arthritis treated with IV golimumab. Additionally, pharmacokinetic and clinical response data from five patients with jPsA in GO-VIVA were comparable to those in adults with PsA treated with IV golimumab. No new safety signals were observed in GO-VIVA. Pharmacokinetic and clinical response data observed in the four pediatric patients with PsO and jPsA treated with ustekinumab in CADMUS and CADMUS Jr were similar to those in the 91 pediatric patients with PsO without jPsA in these trials and to those in adults with PsA treated with ustekinumab. Safety was extrapolated from CADMUS or CADMUS Jr; no new signals were observed.ConclusionsThese three sets of analyses corroborate similar exposure and efficacy of IV golimumab in pediatric patients with pc-JIA or jPsA and SC ustekinumab in patients with jPsA to support extrapolation of established adult efficacy. The overall safety profiles of IV golimumab in pediatric patients with pc-JIA or jPsA and SC ustekinumab in pediatric patients with PsO with or without jPsA were consistent with the safety profiles of these agents in the context of their clinical programs and cumulative use. Based on these analyses, the US Food and Drug Administration approved IV golimumab for polyarticular JIA and active PsA in patients 2 years and older and SC ustekinumab for pediatric PsA in patients 6 years and older, highlighting how use of an extrapolation approach can help streamline drug development for pediatric patient populations in whom larger clinical trials are not feasible.Clinical Trial RegistrationGO-VIVA (NCT02277444) was registered at clinicaltrials.gov on 29 October 2014; CADMUS (NCT01090427) was registered on 22 March 2010; and CADMUS Jr (NCT02698475) was registered on 3 March 2016.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40272-022-00533-y.

POS1077 LARGE JOINT INVOLVEMENT AND SUBSTANTIAL DISEASE BURDEN IN PATIENTS WITH OLIGOARTICULAR AND POLYARTICULAR PSORIATIC ARTHRITIS IN THE MULTINATIONAL UPLIFT SURVEY

BackgroundPatients (pts) with oligoarticular psoriatic arthritis (PsA) report quality-of-life impairment similar to polyarticular PsA pts despite less joint involvement. In the 2020 Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey, we evaluated other aspects of disease burden in pts with oligoarticular (≤4 joints) and polyarticular (&gt;4 joints) PsA.ObjectivesTo explore joint involvement distribution and relative disease burden in pts with self-reported healthcare provider (HCP)–diagnosed PsA who self-identified with oligoarticular vs polyarticular joint involvement.MethodsUPLIFT was a multinational Web-based survey in adults who reported an HCP diagnosis of PsA and/or psoriasis. This analysis evaluated demographics, disease characteristics, joint distribution, and quality-of-life measures in pts with PsA with or without psoriasis with self-identified oligoarticular vs polyarticular joint involvement. Small joint classification includes foot/toes, hands/fingers, and thumbs; intermediate joints includes wrists, elbows, and ankles; and large joints includes shoulders, hips, and knees.ResultsOf the 1256 pts with PsA completing the survey, 44% had oligoarticular PsA and 56% polyarticular PsA. The polyarticular PsA group had higher mean age, fewer males, and more pts with body mass index ≥25 kg/m2 (Table 1). Prevalence of depression, hypertension, and diabetes was generally similar between groups (Table 1). In pts with oligoarticular and polyarticular PsA, respectively, involvement of large joints was most prevalent (63%, 91%), followed by intermediate (46%, 87%) and small (20%, 76%) joints. Axial involvement was less prevalent in pts with oligoarticular (30%) vs polyarticular (67%) PsA. Common areas of joint involvement were the knees, elbows, and shoulders for oligoarticular PsA pts and the knees, hands, and elbows for polyarticular PsA pts (Figure 1). Involvement in the hands, wrists, thumbs, feet, and ankles was proportionately greater in polyarticular pts vs oligoarticular pts. Dactylitis, enthesitis, and nail disease, respectively, were each present in approximately one third of oligoarticular PsA pts and more than half of polyarticular PsA pts. Mean Patient Assessment of PsA Severity, Health Assessment Questionnaire (HAQ)-8, and Psoriatic Arthritis Impact of Disease 12-item (PSAID-12) scores indicated similar disease burden between the two groups (Table 1). In both groups, &gt;70% reported an unacceptable PsA symptom state (PSAID &gt;4), and &gt;60% had Patient Health Questionnaire 2-item (PHQ-2) score ≥3, consistent with positive screening for depression (Table 1).Table 1.Demographics and Patient CharacteristicsOligoarticular PsA (n=550)Polyarticular PsA (n=706)Age, mean (SD), y39.5 (15.23)45.6 (14.89)Male sex, n (%)327 (60)347 (49)Body mass index ≥25 kg/m2 (overweight/obese), n (%)164 (30)292 (41)PsA duration, mean (SD), y11.1 (10.44)13.8 (11.40)PsA treatment use, n (%)*Prior oral prescription231 (44)217 (31)Prior injectable/intravenous177 (34)169 (24)Current oral prescription185 (35)364 (53)Current injectable/ intravenous154 (29)246 (36)Comorbidities, n (%)Hypertension230 (42)302 (43)Depression214 (39)291 (41)Diabetes201 (37)236 (33)Skin or non-skin cancer200 (36)168 (24)Heart disease149 (27)123 (17)Inflammatory bowel disease156 (28)142 (20)Liver disease149 (27)98 (14)Patient Assessment of PsA Severity, mean, (SD)5.0 (2.92)5.7 (2.53)HAQ-8, mean, (SD)0.9 (0.65)0.8 (0.64)PSAID-12, mean, (SD)5.3 (2.54)5.6 (2.42)PSAID &gt;4, n (%)389 (71)533 (76)PHQ-2 ≥3, n (%)383 (70)452 (64)*n=525 with oligoarticular PsA; n=691 with polyarticular PsA.ConclusionIn the UPLIFT survey, almost half of pts with PsA self-identified with oligoarticular PsA. Both oligoarticular and polyarticular PsA groups experienced similar levels of disease burden, including a high prevalence of an unacceptable PsA symptom state and a PHQ-2 score ≥3, indicative of a positive screen for depression.AcknowledgementsThe authors gratefully acknowledge Hsiuan Lin Wu for data analysis. This study was funded by Amgen Inc. Writing support was funded by Amgen Inc. and provided by Kristin Carlin, BSPharm, MBA, of Peloton Advantage, LLC, an OPEN Health company, and Cathryn M. Carter, MS, employee of and stockholder in Amgen Inc.Disclosure of InterestsWilliam Tillett Speakers bureau: AbbVie, Amgen Inc., Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen Inc., Celgene, Eli Lilly, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, and Janssen, Alexis Ogdie Consultant of: AbbVie, Amgen Inc., Bristol Myers Squibb, Celgene, CorEvitas’ Psoriatic Arthritis/Spondyloarthritis Registry (formerly Corrona), Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen Inc., Novartis, and Pfizer, Pascal Richette Speakers bureau: AbbVie, Amgen Inc., Bristol Myers Squibb, Janssen, Lilly, Novartis, Pfizer, and UCB, Alice B Gottlieb Consultant of: Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, LEO Pharma, Eli Lilly, Novartis, Sun, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun, UCB, and Xbiotech, Shauna Jardon Shareholder of: Stock ownership in Amgen Inc, Employee of: Employee of Amgen Inc, Sven Richter Shareholder of: Stock ownership in Amgen at time of study, Employee of: Employment by Amgen at time of study, Andrea Flower Employee of: Employment by ProUnlimited, under contract for Amgen Inc., Joseph Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, EMD, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Serono, Sun, and UCB

B Cells on the Stage of Inflammation in Juvenile Idiopathic Arthritis: Leading or Supporting Actors in Disease Pathogenesis?

Juvenile idiopathic arthritis (JIA) is a term that collectively refers to a group of chronic childhood arthritides, which together constitute the most common rheumatic condition in children. The International League of Associations for Rheumatology (ILAR) criteria define seven categories of JIA: oligoarticular, polyarticular rheumatoid factor (RF) negative (RF-), polyarticular RF positive (RF+), systemic, enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. The ILAR classification includes persistent and extended oligoarthritis as subcategories of oligoarticular JIA, but not as distinct categories. JIA is characterized by a chronic inflammatory process affecting the synovia that begins before the age of 16 and persists at least 6 weeks. If not treated, JIA can cause significant disability and loss of quality of life. Treatment of JIA is adjusted according to the severity of the disease as combinations of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and/ or biological disease modifying anti-rheumatic drugs (DMARDs). Although the disease etiology is unknown, disturbances in innate and adaptive immune responses have been implicated in JIA development. B cells may have important roles in JIA pathogenesis through autoantibody production, antigen presentation, cytokine release and/ or T cell activation. The study of B cells has not been extensively explored in JIA, but evidence from the literature suggests that B cells might have indeed a relevant role in JIA pathophysiology. The detection of autoantibodies such as antinuclear antibodies (ANA), RF and anti-citrullinated protein antibodies (ACPA) in JIA patients supports a breakdown in B cell tolerance. Furthermore, alterations in B cell subpopulations have been documented in peripheral blood and synovial fluid from JIA patients. In fact, altered B cell homeostasis, B cell differentiation and B cell hyperactivity have been described in JIA. Of note, B cell depletion therapy with rituximab has been shown to be an effective and well-tolerated treatment in children with JIA, which further supports B cell intervention in disease development.

O13 Which composite measure best reflects disease activity and predicts treatment change in psoriatic arthritis?

Abstract Background/Aims Multiple composite measures of disease activity are available and used in psoriatic arthritis (PsA) research; however, poor agreement remains amongst clinicians on the optimal measure of disease activity. Research to date has focused on polyarticular PsA, despite oligoarticular disease accounting for around half of cases in clinical practice. We aim to compare the ability of Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), Disease Activity score for PSoriatic Arthritis (DAPSA), GRAppa Composite scorE (GRACE) and Disease Activity Score 28 CRP (DAS28-CRP) to assess disease activity and predict treatment change, amongst usual care patients with oligoarticular and polyarticular psoriatic disease. Methods The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise (GRACE) dataset was utilised. Oligoarthritis was defined as &amp;lt; 5 active joints. Reference measures were clinician and patient opinions on disease control and whether treatment was escalated. Patients with baseline data for all composite measures were included. The ability of each composite measure to predict treatment change and capture disease activity was compared using the Mann-Whitney U test. Results Data were available for 271 patients (152 oligoarthritis, 119 polyarthritis). The mean age, duration of PsA and psoriasis were similar for both groups. A higher proportion of oligoarticular patients were male. Patients with polyarticular disease had higher disease activity in skin, enthesitis and dactylitis. Using both patient and physician definitions of disease control, all composite measures were able to differentiate between patients with active and quiescent disease, regardless of disease subtype (p &amp;lt; 0.05). PASDAS demonstrated the largest differentiation in score. Differences between active and inactive disease scores were more pronounced in oligoarticular disease. PASDAS demonstrated the greatest ability to predict treatment change in both oligoarticular and polyarticular disease. Interestingly, DAPSA could not predict treatment change in polyarticular patients, p = 0.074 (Table 1). Conclusion This is the first study to compare composite measures, in oligoarticular and polyarticular PsA in a multinational cohort. All composite measures of disease activity were able to differentiate between active and inactive disease in both subtypes. PASDAS demonstrated the largest discrimination in both polyarticular and oligoarticular disease, suggesting greatest clinical and research utility. Disclosure L. Tucker: None. P. Helliwell: None. L. Coates: None.

Potential Differences in Clinical Features, Disease Activity, Function and Impact of Disease Between Oligo and Polyarticular Psoriatic Arthritis

Objective: The primary aim of the study was to assess the potential differences in clinical features, disease activity, function and impact of disease between Psoriatic Arthritis (PsA) patients with oligoarticular and polyarticular involvement. Methods: Consecutive PsA patients attending our unit were divided into 2 groups: 1) Oligoarticular (&lt;5 involved joints with or without enthesitic/axial manifestations) and 2) Polyarticular (≥5 joints with or without enthesitic/axial manifestations). A full clinical examination with the assessment of disease characteristics, disease activity (DAPSA, MDA), function (HAQ-DI) and impact of disease (PsAID-12) was performed. Furthermore, a 6-month follow-up evaluation was carried out in order to assess disease differences at baseline and at follow-up. Results: Of the 102 enrolled patients, oligoarticular subset was present in 63 (61.7%), while 39 (38.3%) patients had polyarticular involvement. Patients with oligoarticular subset showed, at baseline evaluation, lower values of global disease activity assessed by physician, HAQ-DI and DAPSA compared to patients with polyarticular pattern. No differences in the impact of disease (PsAID), patient global assessment of disease activity or pain were found. At 6-month follow-up, no significant changes in each group occurred. Conclusion: Our study showed some differences in patients with oligoarticular and polyarticular involvement in terms of disease activity and HAQ-DI, while the overall impact of the disease and the presence of enthesitis, dactylitis and axial disease seem to be similar, with no substantial changes after 6-month follow-up. These results could mean that clinical phenotype might not be responsible for the impact of the disease perceived by the patient.

Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis.

This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity. Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits. At enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = -0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor-negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later. Plasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.

Major differences in medical and surgical treatment of psoriatic arthritis and rheumatoid arthritis: a comparison of two historic cohorts

Objectives Substantial changes in the handling of patients with inflammatory arthritis have occurred during the past half century. Polyarticular psoriatic arthritis (PsA) has been treated with the same synthetic disease-modifying anti-rheumatic drugs (DMARDs) as rheumatoid arthritis (RA), but for PsA there is less documentation regarding their effect. For biologic DMARDs, evidence of effect is more convincing. We have previously investigated the risk of orthopaedic surgery in patients with RA and PsA to see whether the change in treatment over time has improved the long-term outcome of inflammatory arthritis. For RA, patients diagnosed from 1999 onwards had a lower risk of surgery than patients diagnosed in earlier years. For PsA, the risk of surgery did not change similarly. We wished to compare RA patients to PsA patients with regard to medical and surgical treatment. Method We compared a historic cohort of 1010 RA patients diagnosed in 1972–2009 to a historic cohort of 590 PsA patients diagnosed in 1954–2011. Results PsA patients received significantly less medical treatment both in the first year of disease and during the disease course. Risk of surgery during the disease course was lower for PsA than for RA (20% vs 31%). The risk of surgery in RA patients diagnosed from 1999 onwards was similar to that of PsA patients. Conclusions PsA patients received less intensive treatment than RA patients. Their prognosis, regarding orthopaedic surgery, was also less severe. Contrary to RA, the change in treatment did not have beneficial effects regarding the risk of orthopaedic surgery.

Biological disease-modifying antirheumatic drugs in juvenile idiopathic arthritis of polyarticular course, enthesitis-related arthritis, and psoriatic arthritis: a consensus statement.

Juvenile idiopathic arthritis (JIA) is the most common type of inflammatory arthritis in children. Treatment options have been expanded since the introduction of biologics, which are highly effective. The existing local JIA treatment guideline was published more than a decade ago, when use of biologics was not as common. In this article, we review the latest evidence on using biologics in three JIA subtypes: JIA of polyarticular course (pcJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA). Based on the latest information, an update on eligibility, response assessment, termination, and safety information for using biologics in these patients was performed. The JIA Work Group, which consisted of nine paediatricians experienced in managing JIA, was convened in 2016. Publications before July 2017 were screened. Eligible articles were clinical trials, extension studies, systemic reviews, and recommendations from international societies and regulatory agencies about the use of biologics in pcJIA, ERA, and PsA. Evidence extraction, appraisal, and drafting of propositions were performed by two reviewers. Extracted evidence and drafted propositions were presented and discussed at the first two meetings. Overwhelming consensus was obtained at the final meeting in May 2018. Seven practice consensus statements were formulated. Regular review should be performed to keep the practice evidence-based and up-to-date.

Hyaluronan concentration and molecular mass in psoriatic arthritis: biomarkers of disease severity, resistance to treatment, and outcome

Objective: Low molecular mass hyaluronan causes inflammatory processes and can act as a pro-inflammatory cytokine in skin and other sites of activity in psoriatic arthritis (PsA). This study investigated whether the molecular mass distribution of hyaluronan (HA) in skin and the quantity of circulating HA are related to the clinical inflammatory picture in PsA with active disease and to the effect of treatment with anti-tumour necrosis factor-α (anti-TNF-α) adalimumab.Methods: Twenty patients with TNF-α-naïve active polyarticular PsA were included in this prospective clinical trial of treatment with 40 mg s.c. adalimumab according to standard procedure. Clinical activity, patients’ assessments, and skin biopsies were captured at inclusion and at the 12 week follow-up. Ten healthy individuals were recruited for comparison of HA analyses. Histochemistry of skin inflammation, serum HA, and molecular mass of HA were determined.Results: Overall improvements in clinical parameters were observed. Eight of 18 patients reached minimum disease activity after 12 weeks and disease activity was significantly reduced (p < 0.0001). Patients with elevated serum HA values were significantly older, had later onset of arthritis and more deformed joints, still had swollen joints after treatment, and had more circulating inflammatory biomarkers. More severe disease pathology showed a wide spectrum of high-molecular-mass HA accompanied by low mass HA. The treatment appears partly to normalize the HA mass distribution.Conclusion: HA concentration and mass seem to be two possible factors in the inflammatory pathology of PsA acting as biomarkers for disease severity, resistance to treatment, and worse outcome.

The necessity, efficacy and safety of biologics in juvenile idiopathic arthritis.

OBJECTIVE:Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in children. Biologics have changed the faith of children with rheumatic diseases. The main objective of this study was to demonstrate the rate of usage, efficacy and safety of biologics in JIA subtypes.METHODS:This retrospective observational cohort study was conducted between May 2010 and September 2017. All children with the diagnosis of JIA and children under a biological agent treatment were recorded into the local registry system. Age, gender, JIA subtype, medications used, the clinical status of the patient, tuberculosis screening results, and side effects observed under biologics were retrieved from the registry.RESULTS:There were 405 patients with the diagnosis of JIA in the cohort. Biologics were used in 123 (30.3%) JIA patients. Subtype frequencies of JIA patients were as follows: persistent oligoarticular JIA (33.6%), enthesitis-related arthritis (29.2%), systemic JIA (13%), rheumatoid factor (RF)-negative polyarticular JIA (13%), extended oligoarticular JIA (4.2%), RF-positive polyarticular JIA (3.4%), psoriatic arthritis (1.8%) and unclassified arthritis (1.8%). The rate of biologic use was high in extended oligoarticular JIA (64.7% of the cases), RF-positive polyarticular JIA (57.1%), psoriatic arthritis (57.1%), RF-negative polyarticular JIA (41.5%), and in systemic JIA (39.6%). Enthesitis-related arthritis (27.1%), persistent oligoarticular JIA (17.6%) and unclassified arthritis (16.6%) patients were the cases that needed a biologic agent in the last order. At the last control, 78.9% of the cases were in remission, while 21.1% of them were active despite biologic treatment. Isoniazid prophylaxis was used in 30.8% of the patients. None of the patients developed active tuberculosis infection under prophylaxis. Adverse events were observed in 18.6% of patients under biologics as recurrent uncomplicated upper respiratory tract infections being the most common.CONCLUSION:Biologics are safe and effective treatment options in children with JIA. Most of the JIA patients with polyarticular involvement require biologics earlier in the disease course. The risk of tuberculosis infection seems not to be increased after appropriate screening and prophylaxis.

Calprotectin strongly and independently predicts relapse in rheumatoid arthritis and polyarticular psoriatic arthritis patients treated with tumor necrosis factor inhibitors: a 1-year prospective cohort study

BackgroundCalprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi.MethodsThis was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28) ≤ 3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL.ResultsNinety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC) = 1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691–0.889) and 0.877 (95% CI 0.772–0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p < 0.001), TNFi TSL (p = 0.004), and PD score (p < 0.001). Univariate Cox regression models showed that time-to-remission/low disease activity (hazard ratio (HR) = 1.17, p < 0.001), calprotectin levels (HR = 2.38, p < 0.001), TNFi TSL (HR = 0.47, p = 0.018), and PD score (HR = 1.31, p < 0.001) were significantly associated with disease relapse. In the multivariate analysis, only baseline calprotectin levels independently predicted disease relapse (HR = 2.41, p = 0.002). The generalized estimating equation analysis showed that only disease activity by DAS28-erythrocyte sedimentation rate (ESR) was significantly associated with longitudinal changes in TNFi TSL (regression coefficient 0.26 (0.0676 to 0.0036), p = 0.001).ConclusionTime-to-remission/low disease activity, calprotectin serum levels, TNFi TSL, and PD score were significantly associated with disease relapse. However, only baseline calprotectin serum levels independently predicted disease relapse in RA and PsA patients under TNFi therapy.

Early Psoriatic Arthritis Versus Early Seronegative Rheumatoid Arthritis: Role of Dermoscopy Combined with Ultrasonography for Differential Diagnosis

Exclusion of psoriatic skin/nail lesions is important in differentiating early seronegative rheumatoid arthritis (ERA) from early polyarticular psoriatic arthritis (EPsA) and such manifestations may go unnoticed in atypical or minimally expressed cases. The aim of this study is to assess the usefulness of integrated rheumatological-dermatological evaluation in highlighting dermatological lesions missed on rheumatological examination and to investigate the role of ultrasonography (US) and dermoscopy in improving the recognition of subclinical psoriatic findings. Patients with a new diagnosis of seropositive or seronegative ERA and EPsA with prevalent hands involvement were recruited. All were reassessed for the presence of psoriatic lesions during an integrated rheumatological-dermatological clinical evaluation and underwent hands US and proximal nailfold dermoscopy. Seventy-three consecutive subjects were included in the study: 25 with seropositive ERA, 23 with seronegative ERA, and 25 with EPsA. One-fourth of the subjects initially diagnosed as seronegative ERA presented cutaneous or nail psoriasis on integrated rheumatological-dermatological evaluation, thereby being reclassified as EPsA. The presence of at least 1 extrasynovial feature on hand US and dotted vessels on proximal nailfold dermoscopy was significantly associated with EPsA, with a sensitivity of 68.0% and 96.0% and a specificity of 88.1% and 83.3% for US and dermoscopy, respectively. When used together, specificity for PsA diagnosis raised to 90.5%. Integrated rheumatological-dermatological clinical evaluation may be helpful in identifying patients with EPsA misclassified as seronegative ERA. Additionally, US and dermoscopy may be used as supportive tools in identifying subclinical psoriatic features, which may come in handy in distinguishing EPsA from ERA.