Association of the clinical components in the distal interphalangeal joint synovio-entheseal complex and subsequent response to ixekizumab or adalimumab in psoriatic arthritis.

OBJECTIVES: To assess the frequency of simultaneous distal interphalangeal (DIP) joint disease and adjacent nail psoriasis (finger unit) among patients with psoriatic arthritis (PsA) and compare the efficacy of the interleukin (IL)-17A antagonist ixekizumab (IXE) and the tumour necrosis factor (TNF)-α inhibitor adalimumab (ADA). METHODS: This post hoc analysis evaluated the simultaneous occurrence of DIP joint involvement (tenderness and/or swelling) and adjacent nail psoriasis among patients with PsA from the SPIRIT-H2H (NCT03151551) trial comparing IXE to ADA. Among patients with simultaneous DIP joint involvement and adjacent nail psoriasis in ≥ 1 digit at baseline, treatment effects were assessed through week 52 for each affected finger unit; 'finger unit' defines the connected DIP joint and adjacent nail of an individual digit. RESULTS: A total of 354 patients had simultaneous DIP joint involvement and adjacent nail psoriasis in ≥ 1 finger unit at baseline. Among them, 1309 (IXE = 639, ADA = 670) finger units had baseline DIP joint tenderness and/or swelling and adjacent nail psoriasis. Proportions of affected finger units achieving complete resolution were significantly higher with IXE vs ADA as early as week 12 (38.8% vs 28.4%, p< 0.0001) and at all post-baseline assessments through week 52 (64.9% vs 57.5%, p= 0.0055). CONCLUSIONS: In this study cohort, patients with DIP joint involvement almost always had adjacent nail psoriasis. Greater resolution of DIP joint tenderness, swelling, and adjacent nail psoriasis was achieved at all timepoints over 52 weeks through targeting IL-17A with IXE than TNF-α with ADA, which is noteworthy given prior comparable musculoskeletal outcomes for both drug classes.

Exploring 5-year changes in general and skin health-related quality of life in psoriatic arthritis patients.

Psoriatic arthritis (PsA) carries a severe disease burden, often leading to deterioration of health-related quality of life (HRQoL). Different comorbidities that are relatively prevalent in PsA are also responsible for compromised HRQoL. To assess real-world data of a 5-year follow-up cohort of PsA patients, focusing on changes in general HRQoL, skin HRQoL, and comorbidities. In this prospective observational study, 114 outpatients diagnosed with PsA were examined at baseline and after 5 years. Data collection included demographics, clinical disease activity measures, and patient-reported outcome measures (PROMs). General HRQoL was assessed with a 15D instrument, and skin HRQoL was assessed with the Dermatology Life Quality Index (DLQI). During the 5-year follow-up, no significant deterioration in HRQoL assessed by 15D (23.53 vs. 23.08, p = 0.85) and DLQI (3.48 vs. 2.68, p = 0.07) was observed. There was no observed decline in other PROMs. The mean total number of comorbidities increased (1.13 vs. 1.39, p < 0.01). A significant improvement in disease activity measures, including 66/68 swollen/tender joint count, Disease Activity Index for Psoriatic Arthritis (all p < 0.01), and Psoriatic Arthritis Severity Index (p = 0.04) was seen. A higher proportion of patients at 5 years were treated with b/tsDMARDs (37.7% vs. 46.5%, p = 0.03). Despite an increased number of comorbidities over 5 years, our PsA cohort showed no decline in HRQoL. This can be attributed to the widespread adoption of modern treatments, leading to improved disease control and the preservation of baseline HRQoL.

Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE.

OBJECTIVES: Evaluate the importance of treatment sequencing in SELECT-COMPARE, assessing potential differences between starting upadacitinib or adalimumab therapy following inadequate MTX response. METHODS: Patients from SELECT-COMPARE were randomized to upadacitinib 15 mg once daily, placebo or adalimumab 40 mg. Per protocol, patients with <20% improvement in tender or swollen joint counts (weeks 14, 18, 22) or failure to achieve Clinical Disease Activity Index (CDAI) low disease activity (LDA) at week 26 were blindly switched from upadacitinib to adalimumab or vice versa. Treatment outcomes, including clinical remission/LDA, physical function, pain and a novel combined endpoint for deep response, were evaluated through 48 weeks and corresponding time-averaged response rates determined. Data were analysed by initial randomized group regardless of any subsequent switch in therapy. RESULTS: This post hoc analysis included 651 patients initially randomized to upadacitinib (of whom 252 switched to adalimumab) and 327 patients initially randomized to adalimumab (of whom 159 switched to upadacitinib). At week 48, patients randomized to either therapy demonstrated similar achievement of most treatment endpoints. Greater improvements in the total time spent in a lower disease state were observed for initial upadacitinib vs initial adalimumab therapy across most clinical and patient-reported outcomes through 48 weeks, and the median time to DAS28(CRP) <2.6/≤3.2 occurred 6-8 weeks earlier among those randomized to upadacitinib. CONCLUSION: Following a modified treat-to-target strategy, rates of CDAI remission/LDA and DAS28(CRP) <2.6/≤3.2 at 48 weeks were similar, regardless of starting therapy. However, patients initially receiving upadacitinib reached treatment targets more quickly and spent more time in clinical targets over the initial 48 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02629159.

Management of Concomitant Inflammatory Bowel Disease or Uveitis in Patients with Psoriatic Arthritis: An Updated Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

Changes of inflammation in patients with psoriatic arthritis after high intensity interval training assessed by ultrasound and MRI, a randomized controlled trial.

BACKGROUND: In psoriatic arthritis (PsA) there is a theoretical risk of increased disease activity related to strenuous physical activity, including exercise. We evaluated the effect of high intensity interval training (HIIT) on objective measures of inflammation in PsA assessed by ultrasound (US) of peripheral joints and entheses, and by bone marrow edema (BME) on MRI of the sacroiliac joints (SIJ) and spine. METHODS: We randomly assigned 67 PsA patients to an intervention group that performed structured HIIT for 11 weeks, or to a control group instructed not to change their physical exercise habits. Outcome measures included US evaluation of the total cohort and MRI in a subgroup of 41; both assessed at 3 months. We calculated the proportions with an increased US B-mode and power-doppler (PD) signal of joints and entheses and Spondyloarthritis-Research-Consortium-of-Canada (SPARCC)-BME score of the SIJ and spine for both groups. RESULTS: Proportions with an increased US B-mode score of the joints were 32% and 28% in HIIT and control groups, respectively. Corresponding proportions of PD scores of the joints were 7% and 10% and PD scores of entheses were 32% and 31%. The proportions with increased MRI BME of the SIJ were 6% in the HIIT group and 10% in the control group. Corresponding proportions were 6% and 5% for the MRI BME of the spine. CONCLUSION: In PsA patients with a low to moderate disease activity, there was no clear evidence of objectively measured increased inflammation after HIIT, as evaluated by US and MRI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02995460 (16/12/2016).

Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management.

Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.

Filgotinib, a novel JAK1-preferential inhibitor for the treatment of rheumatoid arthritis: An overview from clinical trials.

In the treatment of rheumatoid arthritis (RA), Janus kinase inhibitors (jakinibs) represent an emerging class of targeted therapies in addition to biologics. The number of jakinibs has been growing and as of 2020, filgotinib was the latest jakinib to enter the international market for treating RA. Filgotinib has demonstrated preferential inhibition of JAK1-dependent cytokine signaling in in vitro assays. It has been evaluated in the DARWIN (phase 2) and FINCH (phase 3) series of clinical studies for treating patients with moderately-to-severely active RA. Filgotinib received regulatory approval in Japan and Europe in September 2020, while in August 2020 the United States Food and Drug Administration requested additional data from two ongoing clinical studies assessing the potential impact of filgotinib on sperm parameters. This article will review the pharmacological properties, efficacy, and safety of filgotinib as demonstrated in clinical studies. Expert opinion will be provided on jakinibs for RA treatment from the viewpoints of basic research and clinical practice.

Bimekizumab in patients with active psoriatic arthritis: results from a 48-week, randomised, double-blind, placebo-controlled, dose-ranging phase 2b trial.

BACKGROUND: Dual neutralisation of interleukin 17A (IL17A) and interleukin 17F (IL17F) is a potential novel therapeutic approach in psoriatic arthritis. We assessed bimekizumab, a monoclonal antibody that selectively neutralises IL17A and IL17F, in patients with active psoriatic arthritis. METHODS: BE ACTIVE was a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study done at 41 sites in the Czech Republic, Germany, Hungary, Poland, Russia, and the USA. Eligible patients aged 18 years or older with active adult-onset psoriatic arthritis and symptoms for at least 6 months were randomly assigned (1:1:1:1:1) to placebo, 16 mg bimekizumab, 160 mg bimekizumab, 160 mg bimekizumab with a one-off 320 mg loading dose, or 320 mg bimekizumab, which were administered as subcutaneous injections every 4 weeks for 12 weeks. After 12 weeks, patients assigned to the placebo and 16 mg bimekizumab groups were randomly reassigned (1:1) to either 160 mg or 320 mg bimekizumab, and all other patients remained on their originally assigned initial dose up to 48 weeks. Both participants and researchers were blinded to treatment allocation in the first 12 weeks, and blinded to the dose of bimekizumab thereafter. The primary endpoint was the proportion of patients with at least 50% improvement in the American College of Rheumatology response criteria at week 12, which was assessed in all patients who received at least one dose of study treatment and had a valid measurement of the primary efficacy endpoint at baseline. The trial, including all follow-up, has been completed. This trial is registered with ClinicalTrials.gov, NCT02969525. FINDINGS: Between Oct 27, 2016, and July 16, 2018, 308 patients were screened, and 206 were randomly assigned: 42 to the placebo group, and 41 each to the four bimekizumab groups. At 12 weeks, compared with the placebo group, significantly more patients in the 16 mg bimekizumab (odds ratio [OR] 4·2 [95% CI 1·1-15·2]; p=0·032), 160 mg bimekizumab (8·1 [2·3-28·7]; p=0·0012), and 160 mg (loading dose) bimekizumab (9·7 [2·7-34·3]; p=0·0004) groups achieved an ACR50 response. At 12 weeks, 24 (57%) of 42 patients in the placebo group and 68 (41%) of the 164 patients in the bimekizumab groups reported treatment-emergent adverse events. Most of these adverse events were mild or moderate. Serious treatment-emergent adverse events occurred in nine patients, eight of whom were receiving bimekizumab. No deaths or cases of inflammatory bowel disease were reported. INTERPRETATION: Bimekizumab doses of 16 mg and 160 mg (with or without a 320 mg loading dose) were associated with significant improvements in ACR50 compared with placebo, with an acceptable safety profile. Our results support phase 3 investigation of bimekizumab as a treatment for psoriatic arthritis. FUNDING: UCB Pharma.

Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial.

BACKGROUND: Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. METHODS: This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080. FINDINGS: Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. INTERPRETATION: Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. FUNDING: Novartis Pharma.

Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

GRAPPA Treatment Recommendations: An Update From the 2020 GRAPPA Annual Meeting.

Throughout 2020, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has been working to update the GRAPPA treatment recommendations for psoriasis and psoriatic arthritis (PsA). The planned methodology for this update was published previously, and herein we provide an update on progress so far, including details of the systematic literature searches undertaken. GRAPPA is committed to regular updates of its treatment recommendations to incorporate the many significant therapeutic advances that have taken place in the PsA literature since the previous recommendation publication in 2015. The development and updating of treatment recommendations for optimal treatment approaches for patients with PsA has been an important mission of the GRAPPA since its inception. GRAPPA is currently finalizing domain-specific recommendations with an aim to produce updated treatment recommendations for publication in 2021.

GRAPPA 2019 Research Recipient Awards Report.

A summary of the research conducted by the recipients of the 2019 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Research Awards is presented. Dr. Alla Ishchenko's project was "Role of Metabolomics in Diagnosis, Disease Severity, and Progression in Psoriasis and Psoriatic Arthritis: A 2-year Prospective Pilot Study" and Dr. Zhenrui Shi's project was "Preclinical Analysis of CCR6 and CCL20 in Mouse and Human Joints, Respectively, as Targets of Therapeutic Intervention in Psoriatic Arthritis."

Effects of Intravenous Golimumab on Health-Related Quality of Life in Patients With Psoriatic Arthritis: 24-Week Results of the GO-VIBRANT Trial.

OBJECTIVES: Evaluate the effects of intravenous golimumab 2 mg/kg on multiple domains of health-related quality of life (HRQoL) in adult patients with active psoriatic arthritis (PsA). METHODS: In this phase III, randomized, double-blinded, placebo-controlled study, adults with active PsA were randomized in a 1:1 ratio to receive intravenous (IV) infusions of placebo (n = 239) or golimumab 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. Physical function was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). HRQoL was assessed using the 36-item Short-Form Health Survey Physical and Mental Component Summary (SF-36 PCS/MCS) scores, the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, EQ VAS, and the Dermatology Life Quality Index (DLQI). RESULTS: Patients in the golimumab group had greater mean changes from baseline in HAQ-DI compared with placebo at weeks 8 (-0.52 vs -0.10), 14 (-0.60 vs -0.12), and 24 (-0.63 vs -0.14). Mean improvements from baseline in SF-36 PCS (8.0 vs 1.7), SF-36 MCS (5.0 vs 1.2), EQ VAS (17.2 vs 3.7), FACIT-Fatigue (7.9 vs 2.0), and DLQI (-7.2 vs -1.7) were also greater in the golimumab group versus placebo at week 8 and were maintained or increased through week 24. Greater proportions of golimumab-treated patients had improvements greater than or equal to the minimal clinically important difference (MCID) for HAQ-DI, SF-36 PCS/MCS, EQ VAS, FACIT-Fatigue, and DLQI scores at weeks 14 and 24. CONCLUSION: Improvements in HRQoL were greater in the IV golimumab group compared with placebo and were evident at week 8 and sustained through week 24.

Clinically meaningful improvement in work productivity loss in active psoriatic arthritis: post-hoc analysis of SPIRIT-P1 and SPIRIT-P2 trials.

OBJECTIVES: To determine the proportion of patients in Phase 3 studies (SPIRIT-P1 and SPIRIT-P2) who achieved minimal clinically important difference (MCID) for work productivity loss and activity impairment domains of Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire. METHODS: In the SPIRIT-P1 study, comprising a 24-week double-blind treatment period, biologic-naive patients with active psoriatic arthritis (PsA) were randomised to ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) (starting dose of 160 mg), adalimumab 40 mg every 2 weeks (ADAQ2W), or placebo. SPIRIT-P2 enrolled tumour necrosis factor inhibitor (TNFi)-experienced patients who were randomised to receive IXEQ4W, IXEQ2W or placebo for 24 weeks of double-blind treatment. In this post-hoc analysis, we investigated the proportion of patients in SPIRIT-P1 and P2 studies who achieved 15% improvement in work productivity loss and 20% improvement in activity impairment domains of WPAI-SHP during double- blind treatment period. RESULTS: In SPIRIT-P1, at Week 24, 57.1% and 55.8% of biologic-naive patients on IXEQ4W and ADAQ2W respectively, achieved MCID estimates for work productivity loss compared to 25.6% of patients treated with placebo. The proportion of ixekizumab- and adalimumab-treated patients achieving MCIDs for activity impairment were significantly higher (IXEQ4W: p<0.001; ADAQ2W: p=0.001) com- pared to placebo-treated patients at Week 24. In SPIRIT-P2, significantly more TNFi-experienced patients on IXEQ4W (p<0.001) achieved MCIDs compared to placebo at Week 24. CONCLUSIONS: Treatment with ixekizumab was associated with clinically meaningful improvements in WPAI-SHP domains in biologic-naive and TNFi- experienced patients with active PsA.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

Individual therapeutic DAS28-dcrit responses differentiate between effectiveness of rheumatoid arthritis therapies and reflect patient-reported outcomes: retrospective analysis of DAS28 responses in comparative tocilizumab studies.

Assessment of individual therapeutic responses provides valuable information concerning treatment benefits in individual patients. We evaluated individual therapeutic responses as determined by the Disease Activity Score-28 joints critical difference for improvement (DAS28-dcrit) in rheumatoid arthritis (RA) patients treated with intravenous tocilizumab or comparator anti-tumor necrosis factor (TNF) agents. The previously published DAS28-dcrit value [DAS28 decrease (improvement) ≥ 1.8] was retrospectively applied to data from two studies of tocilizumab in RA, the 52-week ACT-iON observational study and the 24-week ADACTA randomized study. Data were compared within (not between) studies. DAS28 was calculated with erythrocyte sedimentation rate as the inflammatory marker. Stability of DAS28-dcrit responses and European League Against Rheumatism (EULAR) good responses was determined by evaluating repeated responses at subsequent timepoints. A logistic regression model was used to calculate p values for differences in response rates between active agents. Patient-reported outcomes (PROs; pain, global health, function, and fatigue) in DAS28-dcrit responder versus non-responder groups were compared with an ANCOVA model. DAS28-dcrit individual response rates were 78.2% in tocilizumab-treated patients and 58.2% in anti-TNF-treated patients at week 52 in the ACT-ion study (p = 0.0001) and 90.1% versus 59.1% at week 24 in the ADACTA study (p < 0.0001). DAS28-dcrit responses showed greater stability over time (up to 52 weeks) than EULAR good responses. For both active treatments, DAS28-dcrit responses were associated with statistically significant improvements in mean PRO values compared with non-responders. The DAS28-dcrit response criterion provides robust assessments of individual responses to RA therapy and may be useful for discriminating between active agents in clinical studies and guiding treat-to-target decisions in daily practice.

GRAPPA Treatment Recommendations: Updates and Methods.

The development and updating of treatment recommendations for optimal treatment approaches for patients with psoriatic arthritis (PsA) has been an important mission of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) since its inception. Even though the most recent iteration of the GRAPPA PsA recommendations was completed only a few years ago, there have been many significant advances related to therapies and treatment approaches for PsA since their publication. Because of these advances, the process to update the recommendations again has begun. The standard approaches to guideline (or treatment recommendation) development have also evolved in recent years. Herein, the basis for the approach that will be taken for the next version of the GRAPPA PsA treatment recommendations is reviewed.

The contribution of joint and skin improvements to the health-related quality of life of patients with psoriatic arthritis: a post hoc analysis of two randomised controlled studies.

OBJECTIVE: Determine the contribution of joint and skin improvements to health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). METHODS: SPIRIT-P1 and SPIRIT-P2 are phase 3 trials investigating ixekizumab, an interleukin-17A antagonist, in the treatment of patients with active PsA. Patients were randomised to ixekizumab or placebo. Outcomes included the Disease Activity Index for Psoriatic Arthritis (DAPSA), the Psoriasis Area and Severity Index (PASI), the European Quality of Life-Five Dimensions (EQ-5D) Visual Analogue Score (VAS), the 36-Item Short-Form Health Survey (SF-36) and the Work Productivity and Activity Impairment (WPAI) Questionnaire. The contribution of joint and skin improvements to HRQoL was modelled using a smoothing spline method and depicted with response surface graphics. RESULTS: In this integrated analysis, 402 patients with PsA had baseline psoriasis of ≥3% of body surface area. We applied response surface modelling to this patient data set to investigate the relationship between DAPSA, PASI and HRQoL improvements at week 24. The greatest improvement in EQ-5D VAS was associated with the largest per cent improvements in both DAPSA and PASI together, rather than DAPSA or PASI alone. Similar observations were made in domains of SF-36 and WPAI. CONCLUSION: Optimal improvements in patients' HRQoL were dependent on successful treatment of both joint and skin symptoms.

Pro- and anti-inflammatory eicosanoids in psoriatic arthritis.

INTRODUCTION: Eicosanoids are biological lipids that serve as both activators and suppressors of inflammation. Eicosanoid pathways are implicated in synovitis and joint destruction in inflammatory arthritis, yet they might also have a protective function, underscoring the need for a comprehensive understanding of how eicosanoid pathways might be imbalanced. Until recently, sensitive and scalable methods for detecting and quantifying a high number of eicosanoids have not been available. OBJECTIVE: Here, we intend to describe a detailed eicosanoid profiling in patients with psoriatic arthritis (PsA) and evaluate correlations with parameters of disease activity. METHODS: Forty-one patients with PsA, all of whom satisfied the CASPAR classification criteria for PsA, were studied. Outcomes reflecting the activity of peripheral arthritis as well as skin psoriasis, Disease Activity Score (DAS)28, Clinical Disease Index (CDAI) and Body Surface Area (BSA) were assessed. Serum eicosanoids were determined by LC-MS, and the correlation between metabolite levels and disease scores was evaluated. RESULTS: Sixty-six eicosanoids were identified by reverse-phase LC/MS. Certain eicosanoids species including several pro-inflammatory eicosanoids such as PGE2, HXB3 or 6,15-dk,dh,PGF1a correlated with joint disease score. Several eicosapentaenoic acid (EPA)-derived eicosanoids, which associate with anti-inflammatory properties, such as 11-HEPE, 12-HEPE and 15-HEPE, correlated with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) as well. Of interest, resolvin D1, a DHA-derived anti-inflammatory eicosanoid, was down-regulated in patients with high disease activity. CONCLUSION: Both pro- and anti-inflammatory eicosanoids were associated with joint disease score, potentially representing pathways of harm as well as benefit. Further studies are needed to determine whether these eicosanoid species might also play a role in the pathogenesis of joint inflammation in PsA.