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Objectives: To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of IL-17F in addition to IL-17A, vs other biologic and targeted synthetic DMARDs (b/tsDMARDs) for PsA using network meta-analysis (NMA)., Methods: A systematic literature review (most recent update conducted on 1 January 2023) identified randomized controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12-24 for b/tsDMARD-naïve and TNF inhibitor (TNFi)-experienced patients. Safety at Weeks 12-24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank., Results: The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-experienced patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th and 3rd for ACR response ACR20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index 90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-experienced patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events., Conclusion: Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA., Methods: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies., Results: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East., Conclusion: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: To analyze the trends in biologics use at a specialized center over a period of 20 years., Methods: We performed a retrospective analysis of 571 patients diagnosed with psoriatic arthritis enrolled in the Toronto cohort who initiated biologic therapy between January 1, 2000, and July 7, 2020. The probability of drug persistence over time was estimated nonparametrically. The time to discontinuation of first and second treatment was analyzed using Cox regression models, whereas a semiparametric failure time model with a gamma frailty was used to analyze the discontinuation of treatment over successive administrations of biologic therapy., Results: The highest 3-year persistence probability was observed with certolizumab when used as first biologic treatment, while interleukin-17 inhibitors had the lowest probability. However, when used as second medication, certolizumab had the lowest drug survival even when accounting for selection bias. Depression and/or anxiety were associated with a higher rate of drug discontinuation due to all causes (relative risk [RR] 1.68, P = 0.01), while having higher education was associated with lower rates (RR 0.65, P = 0.03). In the analysis accommodating multiple courses of biologics, a higher tender joint count was associated with a higher rate of discontinuation due to all causes (RR 1.02, P = 0.01). Older age at the start of first treatment was associated with a higher rate of discontinuation due to side effects (RR 1.03, P = 0.01), while obesity had a protective role (RR 0.56, P = 0.05)., Conclusion: Persistence in taking biologics depends on whether the biologic was used as first or second treatment. Depression and anxiety, higher tender joint count, and older age lead to drug discontinuation., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Psoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab (SEC) is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials; however, there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC among Canadian patients with PsA., Methods: This was an observational cohort study of Canadian patients with PsA, 18 to 65 years of age, who attended a clinic of the CanSpA network and received treatment with SEC. Patients were indexed on the date they first initiated SEC. Retention was assessed at 12 months postindex. Clinical effectiveness was measured as the proportion of patients in remission and change in disease activity from baseline to 12 months using several clinical indices., Results: In total, 213 patients were included. Overall retention was estimated at 73.6% at 12 months (81.8% for bDMARD- or targeted synthetic DMARD-naïve patients). Out of 110 patients, 17 (15.5%) were in remission based on the Disease Activity Index in Psoriatic Arthritis in 28 joints, and 10 out of 70 patients (14.3%) were in remission based on the Psoriatic Arthritis Disease Activity Score at 12 months. The Psoriasis Area and Severity Index improved by 65.8%; the tender joint count in 68 joints and the swollen joint count in 66 joints improved by 65.5% and 73.7%, respectively., Conclusion: This is the first nationwide study that we know of to describe real-world use of SEC in Canada for PsA, and the results support its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort., Methods: Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity., Results: We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09)., Conclusions: This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis., Competing Interests: Competing interests: All the following relationships are outside the submitted work. AEC—consulting fees from AstraZeneca, Bristol Myers Squibb, Exagen Diagnostics and GlaxoSmithKline (GSK). CG—consulting fees from the Centers for Disease Control (CDC), Morton Grove Pharmaceutical (MGP), Sanofi and UCB. RR-G—consulting fees from GSK, Immuncor and ThermoFisher. DI—consulting fees from Amgen, Merck Serono, AstraZeneca and Eli Lilly (the honoraria are passed onto a local arthritis charity). AR—consulting fees from Lilly. PRF—participation in advisory boards from AbbVie, AstraZeneca and Lilly. MK—consulting fees from GSK. MI—consulting fees from AbbVie, UCB, Novartis, Janssen and Lilly., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objective: Our objective was to assess the effectiveness of conventional and targeted disease-modifying antirheumatic drugs (cDMARDs and tDMARDs, respectively) in treating enthesitis in psoriatic arthritis (PsA)., Methods: Patients with active enthesitis, defined as ≥ 1 tender entheses (of the 29 enthesis sites included in the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Leeds Enthesitis Index, and the Maastricht Ankylosing Spondylitis Enthesitis Score), who were enrolled in a large PsA cohort were included. Medications at baseline were classified into 3 mutually exclusive categories: (1) no treatment or nonsteroidal antiinflammatory drugs (NSAIDs) only; (2) cDMARDs ± NSAIDs; and (3) tDMARDs ± cDMARDs/NSAIDs. Complete resolution of enthesitis (no tender enthesis) at 12 months was the primary outcome. Logistic regression models were developed to determine the association between medication category and enthesitis resolution., Results: Of the 1270 patients studied, 628 (49.44%) had enthesitis. Of these, 526 patients (51.71% males; mean [SD] age 49.02 [13.12] years; mean enthesitis score 2.13 [2.16]; median enthesitis score 2 [IQR 1-2]), with adequate follow-up were analyzed. Complete resolution of enthesitis was noted in 453 (86.12%) patients, within a mean period of 8.73 (3.48) months from baseline. In the regression analysis, though not significant, DMARDs (categories II and III) had higher odds ratios (ORs) compared to category 1 for resolution of enthesitis. Enthesitis resolution was associated with lower joint activity (OR 0.97, 95% CI 0.95-0.99; P = 0.01) and male sex (OR 1.66, 95% CI 0.97-2.84; P = 0.06)., Conclusion: Resolution of enthesitis was observed in 86% of patients in an observational setting regardless of the medication used. Future effectiveness studies may warrant evaluation of enthesitis using advanced imaging., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: We aimed to determine whether the presence of depression or anxiety is associated with the achievement of sustained minimal disease activity (MDA) in patients with psoriatic arthritis (PsA)., Methods: Adult patients satisfying classification criteria for PsA prospectively followed from 2008 to 2017 were included. A standard protocol including physician assessment and patient-reported outcomes determined whether patients achieved sustained MDA, which was defined as meeting MDA criteria for ≥2 consecutive visits. The presence of depression/anxiety was determined using 3 definitions: 1) a score of ≤38 on the mental component summary of the Medical Outcomes Study Short Form 36 (SF-36) health survey, 2) a score of ≤56 on the mental health domain of the SF-36 health survey, and 3) a rheumatologist's report of a diagnosis or treatment for depression/anxiety. A discrete time-to-event analysis was conducted based on a proportional odds model to identify factors associated with achieving sustained MDA., Results: A total of 743 patients were included in the study. The number of patients identified as having depression/anxiety at baseline included 331 patients (44.54%) according to definition 1, 364 patients (48.99%) according to definition 2, and 211 patients (28.4%) according to definition 3. A total of 337 patients (45.36%) did not achieve sustained MDA. The presence of depression/anxiety was associated with reduced probability of achieving sustained MDA, with odds ratio (OR) 0.30 (P < 0.0001), OR 0.34 (P < 0.0001), and OR 0.47 (P < 0.0001) for definitions 1, 2, and 3, respectively. Other variables associated with a reduced probability of achieving sustained MDA included the Charlson comorbidity index and fibromyalgia., Conclusion: Symptoms of anxiety/depression reduce the probability of achieving sustained MDA in PsA. Comprehensive management of PsA should include measures for addressing these comorbidities., (© 2021 American College of Rheumatology.)

Objective: In this post hoc analysis, we examined the potential impact of sex and BMI on response in the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) trial (NCT02376790), a 48-week, phase III, randomized controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept (ETN) monotherapy, and MTX+ETN combination therapy in patients with psoriatic arthritis (PsA) who were naïve to MTX and biologics., Methods: We evaluated key outcomes at week 24 stratified by sex (male vs female) and BMI (kg/m 2 ; ≤ 30 vs > 30), including the American College of Rheumatology 20 (ACR20) criteria, minimal disease activity (MDA), very low disease activity (VLDA), and Psoriatic Arthritis Disease Activity Score (PASDAS). We analyzed data using descriptive statistics, normal approximation, logistic model, and analysis of covariance., Results: A total of 851 patients completed the SEAM-PsA trial. Higher proportions of men than women who received MTX+ETN combination therapy achieved ACR20 (71.5% vs 58.3%; P = 0.02), MDA (45.8% vs 25.2%; P = 0.0003), and VLDA (19.1% vs 9.5%; P = 0.03), and men achieved better PASDAS (-3.0 vs -2.3; P = 0.0004). Patients with BMI ≤ 30 generally had better outcomes than those with BMI > 30 in some treatment arms for ACR20, MDA, VLDA, and PASDAS; however, there was no consistent pattern regarding the treatment arm in which the difference occurred., Conclusion: Improved outcomes were observed more in men than in women for MDA and PASDAS with MTX+ETN combination therapy. Patients with BMI ≤ 30 had better outcomes than those with BMI > 30, with no clear pattern regarding treatment received. These findings suggest that contextual factors such as sex and BMI may affect response to PsA therapy., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: The probability of achieving Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) treatment targets (remission [REM], low disease activity [LDA]) was evaluated following apremilast monotherapy in disease-modifying antirheumatic drug (DMARD)-naïve patients with psoriatic arthritis (PsA) based on baseline disease activity., Methods: This post hoc probability analysis of PALACE 4, a phase III, multicenter, randomized, placebo-controlled study, evaluated shifting across cDAPSA categories from baseline to week 52 and included DMARD-naïve patients receiving apremilast 30 mg BID with available baseline cDAPSA data. Changes in articular/extraarticular manifestations were evaluated in patients with week 52 cDAPSA components. cDAPSA treatment target achievement was assessed in a subgroup with baseline extraarticular PsA manifestations (skin involvement, enthesitis, dactylitis)., Results: Of 175 apremilast-treated patients in the probability analysis, 66.3% were in high disease activity (HDA) and 31.4% in moderate disease activity (ModDA) at baseline. Approximately twice as many patients in ModDA at baseline reached REM/LDA at week 52 vs those in HDA (61.7% vs 28.2%). Achieving cDAPSA treatment targets was associated with reductions in articular (swollen/tender joints) and extraarticular (skin involvement, enthesitis, dactylitis, functional disability) disease activity. Similar treatment target achievement rates were observed in the subgroup with ≥ 1 extraarticular PsA manifestation (n = 126; ModDA: 66.7%, HDA: 32.2%)., Conclusion: Apremilast-treated patients with baseline ModDA had higher probability of achieving cDAPSA treatment targets than patients with HDA. Resolution and/or near resolution of articular and/or extraarticular PsA manifestations was achieved by patients in REM/LDA at week 52. Consistent treatment target achievement was observed in patients with 1 or multiple extraarticular manifestations of active PsA., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: Multiple guidelines recommend continuing hydroxychloroquine (HCQ) for SLE during pregnancy based on observational data. The goal of this individual patient data meta-analysis was to identify the potential benefits and harms of HCQ use within lupus pregnancies., Methods: Eligible studies included prospectively collected pregnancies in women with lupus. After a systematic literature search, seven datasets meeting inclusion criteria were obtained. Pregnancy outcomes and lupus activity were compared for pregnancies with a visit in the first trimester in women who did or did not take HCQ throughout pregnancy. Birth defects were not systematically collected. This analysis was conducted in each dataset, and results were aggregated to provide a pooled OR., Results: Seven cohorts provided 938 pregnancies in 804 women. After selecting one pregnancy per patient with a first trimester visit, 668 pregnancies were included; 63% took HCQ throughout pregnancy. Compared with pregnancies without HCQ, those with HCQ had lower odds of highly active lupus, but did not have different odds of fetal loss, preterm delivery or pre-eclampsia. Among women with low lupus activity, HCQ reduced the odds of preterm delivery., Conclusions: This large study of prospectively-collected lupus pregnancies demonstrates a decrease in lupus activity among woman who continue HCQ through pregnancy and no harm to pregnancy outcomes. Like all studies of HCQ in lupus pregnancy, this study is confounded by indication and non-adherence. As this study confirms the safety of HCQ and diminished SLE activity with use, it is consistent with current recommendations to continue HCQ throughout pregnancy., Competing Interests: Competing interests: MC: Funding: AHRQ, Arthritis Foundation; Grants: GSK; Consulting and Advisory Board: UCB. AE: Grant funding: NIH NCATS Award 1KL2TR002554. SB: Grants: NIH, US FDA, PCORI, RRF, CARRA; Consulting: UCB; Travel: FDA; Leadership: CARRA Assistant Scientific Director. DDG: Grants and/or consulting fees from AstraZeneca; Leadership: Member of the Systemic Lupus International Collaborating Clinics group; served on the Medical advisory board of the Lupus foundation of America. MAP: Grant NIH RO-1 AR069572., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance., Methods: We analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999-2019). We evaluated person-time contributed while on the initial HCQ dose ('maintenance'), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare., Results: We studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts., Conclusions: SLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful., Competing Interests: Competing interests: All the following relationships are outside the submitted work. Dr AEC: consulting fees from AstraZeneca, Bristol Myers Squibb, Exagen Diagnostics and GlaxoSmithKline. Dr CG: consulting fees from the Centers for Disease Control (CDC), Morton Grove Pharmaceutical (MGP), Sanofi and UCB. Dr RR-G: consulting fees from GSK, Immuncor and ThermoFisher. Dr DAI: consulting fees from Amgen, Merck Serono, AstraZeneca and Eli Lilly (the honoraria are passed onto a local arthritis charity). Dr AR: consulting fees from Lilly. Dr PRF: participation on advisory boards from AbbVie, AstraZeneca and Lilly. Dr MAK: consulting fees from GSK. Dr MI: consulting fees from AbbVie, UCB, Novartis, Janssen and Lilly., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: This study examined the time to clinically meaningful response in patients with active psoriatic arthritis treated with tofacitinib, adalimumab, or placebo switching to tofacitinib., Methods: Data were from two phase 3 studies, OPAL Broaden (12 months) and OPAL Beyond (6 months). Patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks (OPAL Broaden only), or placebo switching to tofacitinib 5 or 10 mg BID at month 3. Baseline to initial response time was according to pre-defined clinically meaningful criteria on Health Assessment Questionnaire-Disability Index (HAQ-DI; ≥ 0.35-point improvement), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; ≥ 4-point improvement), Psoriatic Arthritis Disease Activity Score (PASDAS; post-baseline score ≤ 3.2 and > 1.6-point improvement from baseline), and minimal disease activity (MDA; meeting at least 5 of 7 criteria) composite., Results: In OPAL Broaden, median time to initial HAQ-DI score response was 29, 53, and 30 days in patients treated with tofacitinib 5 mg BID, tofacitinib 10 mg BID, or adalimumab, compared with 162 and 112 days in patients treated with placebo switching to tofacitinib 5 or 10 mg BID at month 3, respectively. Across studies, median time to initial FACIT-F total score response was shorter in patients receiving tofacitinib 5 mg BID (31 days) vs other groups (84-92 days). Median time to initial response was approximately 11 (MDA)/6-9 months (PASDAS) in tofacitinib/adalimumab groups in OPAL Broaden., Conclusion: This analysis demonstrates tofacitinib's efficacy on most patient-reported and clinical endpoints over time and shows a shorter time to initial, clinically meaningful response in patients receiving tofacitinib vs patients switching from placebo to tofacitinib., Trial Registration: ClinicalTrials.gov , NCT01877668. Registered June 12, 2013. ClinicalTrials.gov , NCT01882439. Registered June 18, 2013., (© 2022. The Author(s).)

Background: In psoriatic arthritis (PsA), further understanding of the relationships between clinical measures and patient-reported outcomes (PROs) is needed. This post hoc analysis evaluated associations between minimal disease activity (MDA) as a continuous outcome (termed ScoreMDA) or Psoriatic Arthritis Disease Activity Score (PASDAS) with selected PROs not included in the composite measures., Methods: Data from two phase 3 studies of tofacitinib in PsA (OPAL Broaden [NCT01877668; N = 422]; OPAL Beyond [NCT01882439; N = 394]) were included. MDA (binary outcome) was defined as meeting ≥5/7 criteria. For ScoreMDA, each criterion was assigned a value (1 = true; 0 = false; score range, 0-7; scores ≥5 indicated MDA). For PASDAS (score range, 0-10), higher scores indicated worse disease activity. PROs analyzed included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Patient's Assessment of Arthritis Pain visual analog scale (Pain VAS), and EuroQoL-Five Dimensions-Three Level Health Questionnaire visual analog scale (EQ-5D-3L VAS) and utility index. Relationships were evaluated using repeated measures regression models., Results: Similar, approximately linear relationships were confirmed between PASDAS or ScoreMDA and PROs in both studies. In OPAL Broaden and OPAL Beyond, a one-point difference in PASDAS was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (- 6.7 mm, - 6.9 mm), Pain VAS (9.9 mm, 10.7 mm), and FACIT-F (- 2.8, - 3.3). A one-point difference in ScoreMDA was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (5.0 mm, 5.5 mm) and FACIT-F (1.9, 2.7) in OPAL Broaden and OPAL Beyond, respectively., Conclusions: Linear associations between PASDAS or ScoreMDA and PROs provide interpretable and quantifiable metrics between composite clinical measures and PROs, highlighting the importance of these measures in understanding the relevance of treat-to-target goals in PsA., Trial Registration: ClinicalTrials.gov, NCT01877668 . Registered on June 12, 2013. ClinicalTrials.gov, NCT01882439 . Registered on June 18, 2013.

Objectives: To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA., Methods: The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS)., Results: At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments., Conclusion: PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden., Trail Registration: https://ClinicalTrials.gov, number NCT02376790., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To analyse the onset and sustainability of patient-reported improvements in symptoms of psoriatic arthritis (PsA) following treatment with ixekizumab (IXE) up to Week 108., Methods: In patients with active PsA, either naive to biological DMARDs (SPIRIT-P1) or having inadequate response or intolerance to 1 or 2 prior TNF-inhibitors (TNFi‑experienced; SPIRIT-P2), we analysed the change from baseline in joint pain visual analogue scale (VAS; 0-100 scale), patient global assessment (PatGA VAS; 0-100 scale), fatigue numerical rating scale (NRS; 0 [no fatigue] to 10 [worst imaginable]), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3), up to Week 108., Results: IXE-treated patients compared to placebo reported rapid and statistically significant improvement in pain VAS, PatGA, and HAQ-DI as early as Week 1 and this benefit was sustained or increased through Week 108. Fatigue scores improved in IXE-treated patients compared to placebo in both studies; results were statistically significant at Week 24 only in SPIRIT-P2. Improvements in fatigue with IXE were sustained over 2 years. The improvements observed in these patient-reported outcomes (PROs) were consistent in biologic-naive or TNFi-experienced patients., Conclusions: Patients treated with IXE versus PBO achieved significantly greater improvements and showed faster onset of improvements in patient-reported outcomes measuring symptoms and impact of PsA. Responses were sustained over 2 years and were generally consistent regardless of prior TNFi experience.

Biological therapies have dramatically improved the therapeutic landscape of psoriatic arthritis (PsA); however, 40-50% of patients are primary non-responders with response rates declining significantly with each successive biological therapy. Therefore, there is a pressing need to develop a coherent strategy for effective initial and subsequent selection of biologic agents. We interrogated 40 PsA patients initiating either tumour necrosis factor inhibitors (TNFi) or interleukin-17A inhibitors (17Ai) for active PsA. Patients achieving low disease activity according to the Disease Activity Index for PsA (DAPSA) at 3 months were classified as responders. Baseline and 3-month CD4 + transcript profiling were performed, and novel signaling pathways were identified using a multi-omics profiling and integrative computational analysis approach. Using transcriptomic data at initiation of therapy, we identified over 100 differentially expressed genes (DEGs) that differentiated IL-17Ai response from non-response and TNFi response from non-response. Integration of cell-type-specific DEGs with protein-protein interactions and further comprehensive pathway enrichment analysis revealed several pathways. Rho GTPase signaling pathway exhibited a strong signal specific to IL-17Ai response and the genes, RAC1 and ROCKs, are supported by results from prior research. Our detailed network and pathway analyses have identified the rewiring of Rho GTPase pathways as potential markers of response to IL17Ai but not TNFi. These results need further verification.

Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling., Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model., Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6-18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0., Conclusion: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies., (© 2020, American College of Rheumatology.)

Objectives: Physical function (PF) is a core domain to be measured in randomized controlled trials (RCTs) of psoriatic arthritis (PsA), yet the discriminative performance of patient reported outcome measures (PROMs) for PF in RCTs has not been evaluated systematically. In this systematic review, we aimed to evaluate the clinical trial discrimination of PF-PROMs in PsA RCTs., Methods: We searched PubMed and Scopus databases in English to identify all original RCTs on biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) conducted in PsA. We assessed quality in each article using the OMERACT good method checklist. Effect sizes (ES) for the PF-PROMs were calculated and appraised using a priori hypotheses. Evidence supporting clinical trial discrimination for each PF-PROM was summarized to derive recommendations., Results: 35 articles from 31 RCTs were included. Four PF-PROMs had data for evaluation: HAQ-Disability Index (DI), HAQ-Spondyloarthritis (S), and Short Form 36-item Health Survey Physical Component Summary (SF-36 PCS) and Physical Functioning domain (SF-36 PF). As anticipated, higher ES values were observed for intervention groups than the control groups. Across all studies, for HAQ-DI, the median ES were -0.73 and -0.24 for intervention and control groups, respectively. Whereas for SF-36 PCS, the median ES were 0.77 and 0.23. For intervention and control groups, respectively., Conclusion: Clinical trial discrimination was supported for HAQ-DI and SF-36 PCS in PsA with low risk of bias; and for SF-36 PF and HAQ-S with some caution. More studies are required for HAQ-S., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. YYL is funded by the Clinician Scientist award of the National Medical Research Council, Singapore (NMRC/CSA-INV/0022/2017). AMO is funded by the Jerome L. Greene Foundation Scholar Award, the Staurulakis Family Discovery Award, the Rheumatology Research Foundation, and the National Institutes of Health (NIH) through the Rheumatic Diseases Resource-based Core Center (P30-AR053503 Cores A and D, and P30-AR070254, Cores A and B). PH and RC (The Parker Institute, Bispebjerg and Frederiksberg Hospital) is supported by a core grant from the Oak Foundation (OCAY-18–774-OFIL). LCC is funded by a National Institute for Health Research Clinician Scientist award, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). AO is funded by the Rheumatology Research Foundation and NIH/NIAMS R01 AR072363. All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of the funding agencies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA)., Methods: This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0-3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0-6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses., Results: Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24)., Conclusions: At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis., Trial Registration Number: ClinicalTrials.gov: NCT02319759.URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014., Competing Interests: Competing interests: PJM has received research grants or served as a consultant or speaker for AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen Scientific Affairs, Novartis, Pfizer, Sun and UCB.DDG has received consulting fees and/or grant support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB.AD reports grants, personal fees and non-financial support from Janssen, during the conduct of the study; grants and medical writing support from AbbVie and Amgen; grants and personal fees from Eli Lilly; and grants, personal fees and medical writing support from Novartis, Pfizer and UCB.DGM has received research grants from AbbVie, Eli Lilly, Janssen, Novartis and Pfizer and has received honoraria from AbbVie, Celgene, Eli Lilly, Janssen, Pfizer and UCB.PN has received research funding for clinical trials and honoraria for advice and lectures on behalf of Abbvie, BMS, Celgene, MSD, Pfizer, Sanofi, Roche, Janssen, Gilead, UCB, Novartis, and Lilly.W-HB has received personal fees from Janssen, AbbVie, Almirall, Bristol-Myers-Squibb, Celgene, Eli Lilly, Janssen, Leo, Novartis and UCB, and grants from Pfizer.AG has received consulting and/or advisory board fees from AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Incyte, Janssen, Leo, Reddy Labs, Sun Pharmaceutical Industries, UCB, Valeant and Xbiotech, and grants from Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB and Xbiotech.PSH has received research grants from AbbVie, Janssen and Novartis, and has received honoraria from AbbVie, Amgen, Celgene, Galapagos, Pfizer, and UCB.XLX, SX and ECH are employees of Janssen Research & Development, LLC, and own stock in Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary. CSK is an employee of Janssen Global Services, LLC, and owns stock in Johnson & Johnson, of which Janssen Global Services, LLC is a wholly owned subsidiary., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis (PsA). We aimed to validate a cutoff value of PASDAS that defines minimal disease activity (MDA) state, as well as to validate previously defined PASDAS cutoffs for low and high disease activity., Methods: Patients were prospectively recruited from the University of Toronto PsA clinic according to a standard protocol, and variables necessary to complete the PASDAS and the MDA were collected. Receiver-operating characteristic (ROC) curve analysis determined the optimal PASDAS cutoff discriminating patients in MDA state from those not in MDA. Previously proposed PASDAS disease activity cutoff scores were validated by determining the proportion of patients requiring treatment escalation, a surrogate of active disease, in each of low, moderate, and high disease activity groups., Results: One hundred seventy-eight patients [53.9% male, mean PASDAS 3.29 (SD 1.29), 47.8% in MDA] were recruited. ROC curve analysis identified a PASDAS score of 3.2 as the point that maximized the sensitivity and specificity for MDA based on 5 of 7 criteria (sensitivity 88%, specificity 92%, area under the curve 0.96). For MDA based on meeting 6 of 7 and 7 of 7 criteria, PASDAS scores of 2.6 and 2.1 maximized sensitivity and specificity, respectively. An increasing proportion of patients from low to moderate to high disease activity groups required treatment escalation, increasing from 8.1% to 42% to 67%, respectively., Conclusion: A PASDAS score < 3.2 reflects MDA. This study has externally validated PASDAS cutoff scores previously proposed to differentiate between low, moderate, and high disease activity.

Psoriatic arthritis (PsA) is a complex inflammatory musculoskeletal and skin disease. The treatment of PsA has changed substantially over the past 10 years. Clinical practice guidelines are developed to help busy clinicians rapidly integrate evolving knowledge of therapeutic management into practice. In this review, we compare PsA treatment recommendations or guidelines developed by one national organization [ACR and National Psoriasis Foundation (NPF) in 2018], one regional organization (EULAR in 2015), and one international organization (the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis in 2015). We examine the development of guidelines in PsA more broadly and examine similarities and differences in the three sets of recommendations., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To evaluate the effect of baseline risk factors on radiographic progression in patients with active psoriatic arthritis (PsA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and were treated with tofacitinib or adalimumab (ADA)., Methods: Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. OPAL Broaden was a 12-month, double-blind phase III trial. Patients received tofacitinib 5 mg twice daily (BID; n = 107), tofacitinib 10 mg BID (n = 104), or ADA 40 mg once every 2 weeks (n = 106), all with 1 background csDMARD. Radiographs (baseline and Month 12) were scored using the van der Heijde-modified total Sharp score (mTSS) for PsA. Radiographic nonprogression was defined as an increase from baseline in mTSS ≤ 0.5, ≤ 0, or ≤ 0.66. Changes from baseline in mTSS and nonprogression (≤ 0.5 increase from baseline in mTSS) were analyzed by baseline C-reactive protein (CRP) > 2.87 or ≤ 2.87 mg/l. Baseline predictors of radiographic progression were analyzed., Results: At Month 12, > 90% of patients receiving tofacitinib or ADA met all radiographic nonprogression criteria. Mean changes from baseline through Month 12 in mTSS, erosion, and joint space narrowing scores were close to 0. Changes in radiographic outcomes were minimal, irrespective of baseline CRP levels > 2.87 or ≤ 2.87 mg/l, with a small numerical difference observed for tofacitinib 5 mg BID. A significant relationship was observed between baseline CRP level and increases from baseline in mTSS > 0.5 at Month 12., Conclusion: Elevated CRP levels at baseline were associated with greater structural progression. Changes in radiographic outcomes were minimal regardless of CRP levels. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01877668].

Objective: To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA)., Methods: In this double-blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed., Results: Patients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between-group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen., Conclusion: Etanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow-up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College ofRheumatology.)

Objectives: Tofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668])., Methods: Patients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences (MCID); and scores ≥normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments., Results: At month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p≤0.05); SF-36v2 social functioning with 5 mg twice daily (p≤0.05). Percentages reporting improvements ≥MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p≤0.05) and were similar with adalimumab., Conclusion: csDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3., Competing Interests: Competing interests: VS has received consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi and UCB. KdV is a consultant and advisory board member for Pfizer Inc. JAC-C is an investigator for Pfizer Inc. PJM has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc, Sun and UCB; has acted as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Janssen, Lilly, Merck, Novartis, Pfizer Inc, Sun, UCB and Zynerba; and has participated in speakers’ bureaus for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc and UCB. DDG has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc and UCB and has acted as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer Inc and UCB. M-AH, DG, CW and JCC are shareholders and employees of Pfizer Inc. TH is a shareholder, and was an employee, of Pfizer Inc during the time of this analysis.

Objective: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF)., Methods: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations., Results: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment., Conclusion: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA., (© 2018, American College of Rheumatology.)

Objective: To report patient-reported outcomes of patients with PsA treated with ixekizumab up to 52 weeks., Methods: In SPIRIT-P1, biologic-naïve patients with active PsA were randomized to ixekizumab 80 mg every 4 weeks (IXEQ4W; N = 107) or every 2 weeks (IXEQ2W; N = 103) following a 160 mg starting dose, adalimumab 40 mg every 2 weeks (ADA; N = 101) or placebo (PBO; N = 106) during the initial 24-week double-blind treatment period. At week 24 (week 16 for inadequate responders), ADA (8-week washout before starting ixekizumab) and PBO patients were re-randomized to IXEQ2W or IXEQ4W. Patients receiving ixekizumab at week 24 received the same dose during the extension period (EP) to week 52. Patients completed measures including the Dermatology Life Quality Index (DLQI), Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2, European Quality of Life 5 Dimensions Visual Analogue Scale and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem., Results: The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in DLQI at week 24; 22% (PBO), 53% (IXEQ4W), 63% (IXEQ2W) and 54% (ADA) of patients reported DLQI scores of 0/1. The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2 physical component summary and some domain scores, and European Quality of Life 5 Dimensions Visual Analogue Scale at weeks 12 and 24; and in three of four Work Productivity and Activity Impairment Questionnaire-Specific Health Problem domains at week 24. Results are also presented through week 52 for the EP., Conclusion: In biologic-naïve patients with active PsA, ixekizumab significantly improved skin symptoms, health-related quality of life and work productivity., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239; EU Clinical Trials Register, https://www.clinicaltrialsregister.eu, EudraCT2011-002326-49.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is in the process of selecting core instruments for PsA clinical trials. During a 2-h workshop and breakout group discussions at the GRAPPA 2017 annual meeting in Amsterdam, the Netherlands, participants discussed the first set of candidate instruments to be taken through the OMERACT Filter 2.1 instrument selection process: 66/68 swollen/tender joint count (66/68JC), Spondyloarthritis Consortium of Canada (SPARCC) enthesitis index, patient's global assessment (GRAPPA and OMERACT formulations), Health Assessment Questionnaire-Disability Index (HAQ-DI), Psoriatic Arthritis Impact of Disease (PsAID) questionnaires 9 and 12, and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue. Based on the assessment of domain match (content and face validity) and feasibility according to the OMERACT instrument selection criteria, the working group recommends continuing with appraisal of construct validity and discrimination for 66/68JC, SPARCC, PsAID 9 and 12, HAQ-DI, and FACIT-Fatigue. In addition, it recommends repeating the OMERACT Filter 2.1 process for patient global instruments because of insufficient votes. Additional sets of candidate instruments for the PsA core instrument set will be evaluated in a similar process.

Background: An updated psoriatic arthritis (PsA) core outcome set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016., Objectives: To synthesize the evidence on measurement properties of patient reported outcome measures (PROMs) for PsA and thereby contribute to development of a PsA core outcome measurement set (COMS) as described by the OMERACT Filter 2.0., Methods: A systematic literature search was performed in EMBASE, MEDLINE and PsycINFO on Jan 1, 2017 to identify full-text articles with an aim of assessing the measurement properties of PROMs in PsA. Two independent reviewers rated the quality of studies using the COnsensus based standards for the Selection of health Measurement INstruments (COSMIN) checklist, and performed a qualitative evidence synthesis., Results: Fifty-five studies were included in the systematic review. Forty-four instruments and a total of 89 scales were analyzed. PROMs measuring COS domains with at least fair quality evidence for good validity and reliability (and no evidence for poor properties) included the Stockerau Activity Score for PsA (German), Psoriasis Symptom Inventory, visual analogue scale for Patient Global, 36 Item Short Form Health Survey Physical Function subscale, Health Assessment Questionnaire Disability Index, Bath Ankylosing Spondylitis Functional Index, PsA Impact of Disease questionnaire, PsA Quality of Life questionnaire, VITACORA-19, Functional Assessment of Chronic Illness Therapy Fatigue scale and Social Role Participation Questionnaire., Conclusions: At least one PROM with some evidence for aspects of validity and reliability was available for six of the eight mandatory domains of the PsA COS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To assess the effect of tumor necrosis factor inhibitors (TNFi) on subclinical cardiovascular disease in patients with psoriatic disease., Methods: We performed a 2-stage study. In stage 1, carotid total plaque area was assessed in patients with psoriasis or psoriatic arthritis (PsA) (n = 319) by ultrasound at baseline and after 2-3 years. The annual progression rate of atherosclerosis was the outcome of interest. In stage 2, PsA patients receiving TNFi (n = 21) and age- and sex-matched PsA patients not receiving any biologic agent (n = 13) underwent 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography at baseline and 1 year to assess vascular inflammation, measured as target-to-background ratio (TBR). In both stages, multivariable regression analyses adjusted for cardiovascular risk factors and use of statins were performed., Results: In stage 1, men had significantly higher atherosclerosis progression than women (P < 0.001). TNFi was associated with reduced atherosclerosis progression in men after controlling for cardiovascular risk and use of statins (adjusted β = -2.20 [95% confidence interval -3.41, -1.00], P < 0.001). There was no association between TNFi and atherosclerosis progression in women (P = 0.74). In stage 2, patients receiving TNFi had reduced TBR at 1 year (P = 0.03). Those not receiving TNFi had no significant change in TBR (P = 0.32). The improvement in aortic vascular inflammation in the TNFi group was independent of cardiovascular risk factors (adjusted β = -0.41 [95% confidence interval -0.74, -0.08], P = 0.02)., Conclusion: Our findings indicate that TNFi treatment is associated with reduced progression of carotid plaques in men and improvement in vascular inflammation in both men and women with psoriatic disease., (© 2017, American College of Rheumatology.)

Objective: To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS)., Methods: At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants., Results: We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda., Conclusion: The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

Objectives: To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA)., Methods: This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24., Results: Abatacept significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p<0.001). Although abatacept numerically increased Health Assessment Questionnaire-Disability Index response rates (reduction from baseline ≥0.35) at week 24, this was not statistically significant (31.0% vs 23.7%; p=0.097). The benefits of abatacept were seen in ACR20 responses regardless of tumour necrosis factor inhibitor exposure and in other musculoskeletal manifestations, but significance could not be attributed due to ranking below Health Assessment Questionnaire-Disability Index response in hierarchical testing. However, the benefit on psoriasis lesions was modest. Efficacy was maintained or improved up to week 52. Abatacept was well tolerated with no new safety signals., Conclusions: Abatacept treatment of PsA in this phase III study achieved its primary end point, ACR20 response, showed beneficial trends overall in musculoskeletal manifestations and was well tolerated. There was only a modest impact on psoriasis lesions., Trial Registration Number: ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb)., Competing Interests: Competing interests: PM reports receiving consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Crescendo, Demira, Janssen, Lilly, Merck, Novartis, Pfizer, Sun, UCB and Zynerba; and speaker fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Novartis, Pfizer and UCB. ABG reports receiving consulting fees from Abbott Laboratories (AbbVie), Actelion, Akros, Amgen, Astellas, Baxalta, Beiersdorf, Bristol-Myers Squibb, Canfite, Catabasis, Celgene, Centocor (Janssen), Coronado, CSL Behring Biotherapies for Life, Dermipsor, Genentech, GlaxoSmithKline, Incyte, Karyopharm, Kineta One, KPI Therapeutics, Lilly, Meiji Seika Pharma, Mitsubishi Tanabe Pharma Development America, Novartis, Novo Nordisk, Pfizer, Takeda, TEVA, UCB, Vertex and Xenoport; and research grants (paid to Tufts Medical Center) from Abbott Laboratories (AbbVie), Amgen, Baxalta, Celgene, Centocor (Janssen), Dermira, Levia, Lilly, Merck, Novartis, Pfizer and Xenoport. DvdH reports receiving consultancy fees from Bristol-Myers Squibb and also consultancy fees from AbbVie, Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB (outside the submitted work). OF reports receiving grant support from AbbVie, Bristol-Myers Squibb and Pfizer; and speaker fees from Celgene, Janssen, Novartis and UCB. AJ is an employee of Bristol-Myers Squibb and reports holding stock in Bristol-Myers Squibb. MN is an employee of Bristol-Myers Squibb. SB is an employee of Bristol-Myers Squibb and reports holding stock in Bristol-Myers Squibb. DG reports receiving grant support from Bristol-Myers Squibb to participate in this study; in addition, she reports receiving grant support and fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group recently published the updated 2016 psoriatic arthritis (PsA) core domain set, a set of disease features that should be measured in all clinical trials. At the GRAPPA annual meeting in July 2016, the PsA working group presented the updated PsA core domain set endorsed by 90% of participants at OMERACT in May 2016 and drafted a roadmap for the development of the PsA core outcome measurement set. In this manuscript, we review the development process of the PsA core domain set and the ongoing and proposed work streams for development of a PsA core measurement set.

Objective: To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA)., Methods: Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24., Results: Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7-66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05)., Conclusions: In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo., Trial Registration Number: NCT01695239; EudraCT2011-002326-49; Results., Competing Interests: PJM reports grants and personal fees from Eli Lilly & Company during the conduct of the study. PJM also reports, outside the submitted work, grants, personal fees, and non-financial support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Pfizer and UCB Pharma; grants and personal fees from Merck and Novartis; and non-financial support from Corrona. DvdH reports personal fees from Eli Lilly & Company, during the conduct of the study. DvdH also reports personal fees from AbbVie, Amgen, AstraZeneca, Augurex, Bristol Myers Squibb, Celgene, Centocor, Chugai, Covagen, Daiichi, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex, outside the submitted work. DvdH is the director at Imaging Rheumatology BV. CTR reports personal fees from AbbVie, Amgen, Janssen, Novartis, UCB, Boerhinger Ingelheim, as well as grants from Amgen, outside the submitted work. MO reports grants and non-financial support from Eli Lilly & Company, during the conduct of this study. MO also reports non-financial support from Santen Pharmaceutical, Mitsubishi Tanabe Pharma, Pfizer and Abbott Japan, outside the submitted work. RSC and DKB were employees of Eli Lilly & Company, at the time this study was conducted. CLS, C-YL and CHL are employees of Eli Lilly & Company. DDG reports grants and personal fees from AbbVie, Amgen, Celgene, Janssen, Novartis, Pfizer and UCB, and personal fees from Eli Lilly & Company, outside the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: An international task force has recommended that disease remission or minimal disease activity (MDA) be the target of treatment for psoriatic arthritis (PsA) and that remission or MDA should be attained within 6 months of initiating medication. The aim of this study was to establish the proportion of patients with PsA who achieve MDA after 6 months of methotrexate (MTX) treatment., Methods: Patients who initiated MTX and were naive to biologics between 2004 and 2014 were included. The primary outcome was the achievement of MDA after 6 months of MTX, defined as the presence of at least 5 out of the following 7: tender joint count ≤ 1, swollen joint count (SJC) ≤ 1, Psoriasis Area Severity Index (PASI) ≤ 1 or body surface area ≤ 3%, tender entheseal points ≤ 1, Health Assessment Questionnaire score ≤ 0.5, patient global disease activity visual analog scale (VAS) score ≤ 20, and patient pain VAS ≤ 15. Of 204 patients identified, 167 were treated with MTX for at least 3 months and had sufficient data for analysis at 6 months., Results: At 6 months, 29 patients (17.4%) achieved MDA; 97 patients (58.1%) achieved an SJC ≤ 1 and 138 (82.6%) a PASI ≤ 1. Only 22 (13.2%) achieved the patient global disease activity criterion. Lower back pain and dactylitis were associated with a lower probability of achieving MDA., Conclusion: MTX use achieves MDA by 6 months in < 20% of patients. This compares unfavorably with data for tumor necrosis factor inhibitor use.

Objective: To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA)., Methods: GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire., Results: Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema., Conclusion: We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves., (© 2016, American College of Rheumatology.)

Objective: To discuss the need for revision of the "core set" of domains to be included for assessment in psoriatic arthritis (PsA) randomized controlled trials and longitudinal observational studies, review work undertaken since the 2012 meeting of Outcome Measures for Rheumatology 11 (OMERACT 11) to include patient perspectives in this revision, and reassess proposed composite measures in the context of new research data and the OMERACT Filter 2.0 framework., Methods: The OMERACT 12 (2014) PsA working group presented work completed over the last 2 years to incorporate patient involvement in PsA outcomes research, review the endorsed PsA core set based on the patient perspective as well as new research findings, and further develop PsA responder indices. Breakout groups then discussed 2 topics: (1) the need to revise the PsA core set, and opportunities to add, move, or merge existing domains to improve existing redundancy; and (2) how to incorporate the core set in a composite index. Breakout groups fed back to the working group before participant voting., Results: Meeting participants endorsed the need to revise the PsA core set according to the OMERACT Filter 2.0 framework (100%), and the inclusion of disease impact (94%) and fatigue (72%) in the inner circle. Breakout group feedback suggested the core set revision was an opportunity to consolidate pathophysiologic aspects such as arthritis, enthesitis, dactylitis, spondylitis as "inflammatory musculoskeletal disease," and nail and skin psoriasis as "psoriasis activity.", Conclusion: Future work will focus on updating the PsA core set and development of responder indices with ongoing, meaningful involvement of patient research partners.

Aim: To assess whether overweight and obese patients with psoriatic arthritis (PsA) are less likely to achieve sustained minimal disease activity (MDA) state compared to patients with normal weight., Methods: A cohort of patients was assessed at the University of Toronto PsA clinic at 6-12-month intervals according to a standard protocol from 2003 to 2012. Patients were categorised into the following groups according to their body mass index (BMI): normal (<25), overweight (25-30), and obese (>30). Sustained MDA was defined as achieving low disease activity state in five or more of the following domains for at least 1 year: skin, enthesitis, tender and swollen joint counts, pain, patient global assessment and function. Proportional odds discrete time to event analysis was used to investigate the association between BMI category and the achievement of sustained MDA., Results: Of the 557 patients included in the study, 36.2% were classified as overweight and 35.4% were obese. Overall, 66.1% of the patients achieved sustained MDA during the follow-up period. A dose-response association was found between obesity and the probability of achieving sustained MDA in the multivariate regression analysis. Patients in the higher BMI categories were less likely to achieve sustained MDA compared those in the lowest BMI category (overweight: OR 0.66 p=0.003; obese: OR 0.53 p<0.0001) after adjusting for potential confounding variables., Conclusions: Overweight and obese patients with PsA are less likely to achieve sustained MDA compared to those of normal weight., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA)., Methods: A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference., Results: Recommendations for the management of SpA were created. Part II: Specific Management Recommendations addresses management with nonpharmacologic methods, nonsteroidal anti-inflammatories and analgesics, disease-modifying antirheumatic drugs, antibiotics, tumor necrosis factor inhibitors, other biologic agents, and surgery. Also included are 10 modifications for application to juvenile SpA., Conclusion: These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that implementation of these recommendations will promote best practices in the treatment of SpA.

Objective: The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA)., Methods: A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference. A survey was sent to the membership of the CRA to obtain an extended review that was used to finalize the recommendations., Results: Guidelines for the management of SpA were created. Part I focuses on the principles of management of SpA in Canada and includes 6 general management principles, 5 ethical considerations, target groups for treatment recommendations, 2 wait time recommendations, and recommendations for disease monitoring. Also included are 6 modifications for application to juvenile SpA., Conclusion: These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that the implementation of these recommendations will promote best practices in the treatment of SpA.

Objectives: Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy., Methods: In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16., Results: At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed., Conclusions: Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated., Clinical Trial Registration Number: NCT01172938.

Aim: To determine whether tumour necrosis factor α (TNFα) blockers are more effective than methotrexate in inhibiting the progression of radiographic joint damage in patients with psoriatic arthritis (PsA)., Methods: A cohort analysis of patients followed prospectively in a large PsA clinic was conducted. Patients who received a TNFα blocker were compared to those treated with methotrexate. Patients who had records of at least 12 months of treatment with either medication for active peripheral PsA and had radiographic bone erosions were analysed. Radiographs of the hands and feet were performed at baseline, 1-2 years (time 1) and 3-4 years (time 2). Radiographic joint damage was scored according to the modified Steinbrocker score. The outcome of interest was the occurrence of radiographic progression. Multivariate logistic regression analysis using generalised estimating equations for repeated measures was used to compare progression in radiographic joint damage between the two treatment groups., Results: 65 patients treated with TNFα blockers and 70 patients treated with methotrexate were analysed. The proportion of patients who demonstrated progression of radiographic damage score at time 1 and time 2 was higher in the methotrexate group compared to the TNFα blockers group (at time 1: 80% vs 58.9% p=0.005; at time 2: 88% vs 61% p=0.005). In the multivariate regression analysis methotrexate treatment was associated with an increase in radiographic damage compared to TNFα blockers (p=0.001)., Conclusions: In a clinic setting, patients with erosive PsA receiving TNFα blockers had a better radiographic outcome compared to those treated with methotrexate.

Objectives: To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis (PsA)., Methods: Adult PsA patients (≥3 swollen, ≥3 tender joints, active psoriasis) were randomly assigned to subcutaneous injections of placebo, golimumab 50 mg or 100 mg every 4 weeks (q4wks) through week 20. All patients received golimumab 50 or 100 mg beginning week 24. Findings through 2 years are reported. Efficacy evaluations included ≥20% improvement in American College of Rheumatology (ACR20) response, good/moderate response in Disease Activity Scores incorporating 28 joints and C-reactive protein (DAS28-CRP), ≥75% improvement in Psoriasis Area and Severity Index (PASI75) and changes in PsA-modified Sharp/van der Heijde scores (SHS)., Results: Golimumab treatment through 2 years was effective in maintaining clinical response (response rates: ACR20 63%-70%, DAS28-CRP 77%-86%, PASI75 56%-72%) and inhibiting radiographic progression (mean change in PsA-modified SHS in golimumab-treated patients: -0.36), with no clear difference between doses. No new safety signals were identified through 2 years. With the study's tuberculosis screening and prophylactic measures, no patient developed active tuberculosis through 2 years., Conclusions: Golimumab 50 and 100 mg for up to 2 years yielded sustained clinical and radiographic efficacy when administered to patients with active PsA. Increasing the golimumab dose from 50 to 100 mg q4wks added limited benefit. Golimumab safety through up to 2 years was consistent with other antitumour necrosis factor α agents used to treat PsA. Treatment of patients with latent tuberculosis identified at baseline appeared to be effective in inhibiting the development of active tuberculosis.

Objective: To identify soluble biomarkers associated with response to therapy with tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA)., Methods: The study was conducted at a PsA clinic where patients are assessed every 6 months, and serum samples are collected and stored once a year at the time of clinical assessment. Forty patients with active PsA who gave serum samples prior to treatment with TNFi and after at least 3 months of therapy were identified. Patients were classified as TNFi responders if tender joint count was < 3, swollen joint count was 0, and Psoriasis Area and Severity Index score was < 4 at the time the second sample was collected. The following biomarkers were tested by ELISA: TNF superfamily 14, matrix metalloprotease-3 (MMP-3), receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, cartilage oligomeric matrix protein (COMP), CPII, C2C and C1-2C, CS-846, and highly sensitive C-reactive protein. Paired t tests and logistic regression was used for statistical analyses., Results: After a mean treatment duration of 11 months with TNFi (etanercept 28 patients, adalimumab 6, golimumab 4, infliximab 2), 29 patients were classified as TNFi responders. Baseline level of MMP-3 was independently associated with responder status (OR 1.067 for each 1-unit increase, p = 0.045). A reduction in MMP-3 levels with therapy increased the odds of achieving response (OR 1.213 for each 1-unit change, p = 0.030), whereas a reduction in COMP decreased the odds (OR 0.587, for each 100-unit increase, p = 0.039). None of the other biomarkers was associated with response., Conclusion: Baseline as well as reduction in serum MMP-3 and increase in serum COMP are independently associated with response to TNFi therapy in patients with PsA.

Objective: To assess whether hydroxychloroquine (HCQ) prevents early damage in patients with systemic lupus erythematosus (SLE)., Methods: We updated an existing systematic review of literature on clinical effects of HCQ in patients with SLE. We conducted a nested case-control study embedded in an inception cohort of patients with SLE. Systemic Lupus International Collaborating Clinics Damage Index (SDI) at 3 years was considered as our primary outcome. Patients with SDI > 0 at 3 years were considered cases and patients with SDI = 0 were controls. Cases and controls were first compared by univariate analysis. Then conditional logistic regression models adjusting for potential confounders were done to study the effect of HCQ on damage accrual., Results: Included in the analysis were 481 patients who had 3 or more years of followup. Out of this cohort, we could match 151 cases with 151 controls. Univariate analysis identified age, the use of any immunosuppressive drugs, HCQ, and cumulative dose of steroids as significant covariates associated with damage accrual. In multivariate analysis, the use of HCQ remained significantly associated with less damage (OR 0.34, 95% CI 0.132-0.867), while age (OR 1.05, 95% CI 1.027-1.078) and a variable combining SLE activity and steroid dose (OR 1.73, 95% CI 1.306-2.295) were associated with damage at 3 years., Conclusion: We demonstrated that HCQ use was associated with less damage at 3 years after diagnosis of SLE when attention was given and adjustment done for disease activity and steroid dose, duration of disease, and calendar year of diagnosis.

Objective: We aimed to determine disease severity and treatment of patients with psoriatic arthritis (PsA) in rheumatology practices in Canada through the PsA Assessment in Rheumatology (PAIR) study., Methods: Rheumatologists who were members of the Canadian Rheumatology Association were asked to complete a form for each patient addressing demographic questions, history, clinical examination, and patient-reported outcomes. Results were compared with a cohort seen in a PsA clinic during the same period., Results: From across Canada, 22 rheumatologists from 5 provinces submitted information about 233 consecutive patients with PsA [145 men (62.2%), 88 women (37.8%), mean age 53.2 yrs (±12.7), 88.4% disease duration>2 yrs]. A majority (80.7%) fulfilled ClASsification for Psoriatic ARthritis (CASPAR) criteria, and 30% had taken no disease-modifying antirheumatic drugs. Clinical joint damage was documented in 60% of the patients, active skin disease in 70%, and nail lesions in 32%. Only 22% were rated as having moderate to high disease activity, while 52% were rated as low disease activity and 26% were deemed in remission. The decision was based on joint counts, patient global assessment, physician global assessment, and acute-phase reactants. Twenty-seven percent of the patients were to have their medications changed based on the current visit, the majority for inadequate response to medications. Patients in the PAIR cohort had more inflamed joints but similar damage to those in the PsA clinic., Conclusion: Patients with PsA seen in regular rheumatology practice fulfill CASPAR criteria, have active disease, and more than half have joint damage. The majority have low activity or are in remission.