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In this randomized trial, secukinumab, an anti–interleukin-17A monoclonal antibody, was more effective than placebo in patients with psoriatic arthritis. Infections, including candida, were more common with secukinumab than with placebo. Psoriatic arthritis is a chronic, systemic inflammatory disease that affects peripheral joints, connective tissues, and the axial skeleton and is associated with psoriasis of the skin and nails. 1 , 2 Inhibitors of tumor necrosis factor (TNF) have significantly improved outcomes among patients with psoriatic arthritis. 3 – 6 However, some patients who have received these agents have not had adequate benefit, have not had a durable response, or have had adverse events. 1 , 2 Effective therapies with a different mechanism of action are needed. Interleukin-17A is postulated to play a role in the pathogenesis of psoriatic arthritis. Increased levels of cells that produce interleukin-17A . . .

ObjectiveTo evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the ‘spondylitis subset’).MethodsAdults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with <5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24.Results256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p<0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p<0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset.ConclusionsIn this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24.Trial registration numberPSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.

Objectives To evaluate prospectively the effect of weight loss on the achievement of minimal disease activity (MDA) in overweight/obese patients with psoriatic arthritis (PsA) starting treatment with tumour necrosis factor α (TNFα) blockers. Methods Among subjects with PsA starting treatment with TNFα blockers, 138 overweight/obese patients received a concomitant dietary intervention (69 a hypocaloric diet (HD) and 69 a free-managed diet (FD)). Changes in metabolic variables were measured and a complete clinical rheumatological evaluation was made in all patients at baseline and after a 6-month follow-up to define the achievement of MDA. Results 126 subjects completed the study. MDA was more often achieved by HD than by FD subjects (HR=1.85, 95% CI 1.019 to 3.345, p=0.043). A diet was successful (≥5% weight loss) in 74 (58.7%) patients. Regardless of the type of diet, after 6 months of treatment with TNFα blockers, ≥5% of weight loss was a predictor of the achievement of MDA (OR=4.20, 95% CI 1.82 to 9.66, p<0.001). For increasing weight-loss categories (<5%, 5–10%, >10%), MDA was achieved by 23.1%, 44.8% and 59.5%, respectively. A higher rate of MDA achievement was found in subjects with 5–10% (OR=3.75, 95% CI 1.36 to 10.36, p=0.011) and in those with >10% (OR=6.67, 95% CI 2.41 to 18.41, p<0.001) weight loss in comparison with those with <5% weight loss. Conclusions Regardless of the type of diet, a successful weight loss (≥5% from baseline values) is associated with a higher rate of achievement of MDA in overweight/obese patients with PsA who start treatment with TNFα blockers.

ObjectivesTo investigate whether a combination of general health (Visual Analogue Scale (VAS)), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain (VAS/Numerical Rating Scale (NRS)), quality of life (EQ-5D), fatigue (VAS/NRS) and presenteeism (0%–100% productivity loss) could aid as a screening tool to detect active disease in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).MethodsRA patients from the tREACH trial and TARA trial (n=683) and PsA patients from the DEPAR cohort (n=525) were included. The association of a deterioration in the aforementioned patient-reported outcome measure (PROM) scores between two consecutive visits and having active disease was assessed. Active disease was defined as a change from disease activity score (DAS) ≤2.4 to DAS >2.4 in RA or Disease Activity Index in Psoriatic Arthritis (DAPSA) ≤14 to DAPSA >14 in PsA. The area under the curve (AUC) of the sum score of deteriorated PROMs was evaluated.Results4594 RA and 1154 PsA visits were evaluated and active disease occurred in 358 (8%) RA and 177 (15%) PsA visits. In both RA and PsA, a deterioration in general health (VAS), HAQ-DI, EQ-5D and pain (VAS/NRS) was significantly associated with active disease. The combination of these PROMs showed acceptable to excellent discriminative ability (RA AUC=0.76, PsA AUC=0.85). If a cut-point of ≥1 deteriorated PROMs is used, 40% of the visits in which RA patients have remission or low disease activity are correctly specified (specificity of 40%), while 10% of visits with active disease are overlooked (sensitivity of 90%). In PsA, these percentages are 41% and 4%, respectively.ConclusionA combination of general health, HAQ-DI, EQ-5D and pain could aid as a screening tool for active disease in patients with RA and PsA. These data could help facilitate remote monitoring of RA and PsA patients in the future.Trial registration numbersISRCTN26791028, NTR2754.

Background Psoriatic arthritis (PsA) is a variable and complex inflammatory condition. Symptoms can compromise physical function, reduce quality of life, and accrue significant health costs. Commonly used patient-reported outcomes largely reflect the professionals’ perspective, however it is not known whether they capture what is important to patients. Objective The aim of our study was to identify treatment outcomes important to patients with PsA. Methods Eight focus groups that were audio recorded, transcribed, anonymised and analysed using inductive thematic analysis were conducted at five hospital sites. The full data set was analysed by the lead researcher, and subsets analysed by three team members (including patient partners). Results Overall, 41 patients sampled for a range of phenotypes and domains of disease activity participated in the study: 20 males; mean age 58 years (range 28–75, standard deviation [SD] 11.4); mean disease duration 9 years (range 0.5–39, SD 8.3); and mean Health Assessment Questionnaire score of 1 (range 0.0–2.5, SD 0.7). Over 60 outcomes were identified and grouped into four themes: (i) symptom alleviation (e.g. pain, fatigue, itchy skin, swelling, and reducing variability); (ii) reduction of disease impact (e.g. tiredness and pain, mobility and dexterity, deteriorating physical fitness, negative emotional responses, and strained relationships and social interactions); (iii) improved prognosis (e.g. slowing down disease progression, maintaining independence, and enhancing quality of life); and (iv) minimisation of treatment harm and burden (e.g. nausea, long-term effects, and administration and monitoring of treatments). Conclusions Outcomes from treatments that are important to patients, which relate to impacts from PsA and its treatment that range beyond those outcomes commonly measured, were identified. These patient perspectives need to be considered when evaluating treatments.

ObjectivesThis post-hoc analysis explored the impact of body mass index (BMI) on tofacitinib efficacy/safety in patients with active psoriatic arthritis (PsA).MethodsData were pooled from two phase 3 studies (NCT01877668; NCT01882439). Analyses included patients randomised to tofacitinib 5/10 mg two times a day or placebo, stratified by baseline BMI: <25 kg/m2, ≥25–<30 kg/m2, ≥30–<35 kg/m2 or ≥35 kg/m2. Endpoints (month 3): American College of Rheumatology (ACR20/50/70), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Psoriasis Area and Severity Index (PASI) 75 response rates; dactylitis/enthesitis resolution rates; changes from baseline Short Form-36 Health Survey version 2 (SF-36v2) Physical/Mental Component Summary (PCS/MCS) scores and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score. Safety was also reported.ResultsAnalysis included 710 patients; 43.8% were obese (BMI ≥30 kg/m2). Tofacitinib demonstrated higher efficacy response rates at month 3, compared with placebo, regardless of baseline BMI. Generally, ACR20/50/70 and HAQ-DI response rates, enthesitis resolution rates and changes from baseline in SF-36v2 PCS score and FACIT-F total score (month 3) were reduced in patients with baseline BMI ≥35 kg/m2 versus patients with lower BMIs. Elevated alanine aminotransferase/aspartate aminotransferase levels were reported in patients with baseline BMI ≥35 kg/m2 receiving tofacitinib 5 mg but not 10 mg two times a day.ConclusionTofacitinib demonstrated greater efficacy than placebo in patients with PsA, regardless of baseline BMI. For all treatment arms, reduced efficacy was observed in patients with baseline BMI ≥35 kg/m2. Safety was generally comparable across BMI categories, although the effect of tofacitinib on liver enzymes in patients with baseline BMI ≥35 kg/m2 was inconclusive.

ObjectiveEvaluate the effect of upadacitinib on pain outcomes in patients with active psoriatic arthritis (PsA) or ankylosing spondylitis (AS) across 3 randomised trials (SELECT-PsA 1 and 2 for PsA; SELECT-AXIS 1 for AS).MethodsPatients were randomised to upadacitinib 15 mg once daily or placebo (all 3 studies), or adalimumab 40 mg every other week (SELECT-PsA 1 only). Pain outcomes included proportion of patients achieving ≥30%, ≥50% and ≥70% reduction from baseline in patient global assessment of pain and other end points.ResultsA higher proportion of patients receiving upadacitinib versus placebo achieved ≥30%, ≥50% and ≥70% reduction in pain end points as early as week 2; these improvements with upadacitinib were generally sustained or increased through year 1 (PsA 1/2 studies: 64%/48%, 58%/42% and 38%/22%, respectively; SELECT-AXIS 1 study: 76%, 72% and 54%). Results were similar with adalimumab in PsA 1 (59%, 49% and 32%). Patients who switched from placebo to upadacitinib 15 mg were able to reach a similar level of improvement as the continuous upadacitinib groups by year 1 (PsA 1/2 studies: 46%–60%, 35%–49% and 15%–34%; AS study: 83%, 72% and 46%). Results were similar with other pain end points.ConclusionRapid and sustained improvements in pain outcomes across several end points were consistently shown with upadacitinib over 1 year in patients with active PsA or AS who had either inadequate response to prior non-biologic or biologic disease-modifying antirheumatic drugs (PsA studies) or were biologic-naïve with inadequate response to non-steroidal anti-inflammatory drugs (AS study).

ObjectivesThis study assessed the psychometric properties of the fatigue numeric rating scale (NRS) and sought to establish values for clinically meaningful change (responder definition).MethodsUsing disease-specific clinician-reported and patient-reported data from two randomised clinical trials of patients with psoriatic arthritis (PsA), the fatigue NRS was evaluated for test–retest reliability, construct validity and responsiveness. A responder definition was also explored using anchor-based and distribution-based methods.ResultsTest–retest reliability analyses supported the reproducibility of the fatigue NRS in patients with PsA (intraclass correlation coefficient=0.829). Mean (SD) values at baseline and week 2 were 5.7 (2.2) and 5.7 (2.4), respectively. Supporting construct validity of the fatigue NRS, moderate-to-large correlations with other assessments measuring similar concepts as measured by Sackett’s conventions were demonstrated. Fatigue severity was reduced when the underlying disease activity was improved and reductions remained consistent at week 12 and 24. A 3-point improvement was identified as being optimal for demonstrating a level of clinically meaningful improvement in fatigue NRS after 12–24 weeks of treatment.ConclusionsFatigue NRS is a valid and responsive patient-reported outcome instrument for use in patients with PsA. The established psychometric properties from this study support the use of fatigue NRS in clinical trials and in routine clinical practice. Robust validation of reliability for use in routine clinical practice in treating patients with active PsA in less active disease states and other more diverse ethnic groups is needed.

BackgroundThe interleukin-12/23p40-subunit-inhibitor ustekinumab significantly improved spondylitis-related symptoms through Week 24 in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (PA-PRS) in PSUMMIT-1&2. We further evaluated ustekinumab’s effect on spondylitis-related endpoints in PSUMMIT-1&2 tumour necrosis factor-inhibitor (TNFi)-naïve patients with PA-PRS.MethodsPatients with active PsA (≥5 swollen and ≥5 tender joints, C-reactive-protein ≥ 3.0 mg/L) despite conventional (PSUMMIT-1&2) and/or prior TNFi (PSUMMIT-2) therapy received subcutaneous ustekinumab 45 mg, 90 mg or placebo (Week 0, Week 4, Week 16). Changes in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) neck/back/hip pain question (#2) and modified BASDAI (mBASDAI, excluding PA) scores and Ankylosing Spondylitis Disease Activity Score (ASDAS) responses were assessed at Weeks 12 and 24.ResultsThe pooled PSUMMIT-1&2, TNFi-naïve (n=747), PA-PRS (n=223) subset (158 with human-leucocyte-antigen (HLA)-B27 results) presented with moderate-to-severe spondylitis-related symptoms (mean BASDAI-neck/back/hip pain-6.51, mBASDAI-6.54, BASDAI-6.51, ASDAS-3.81). Mean Week 24 changes were larger among ustekinumab than placebo-treated patients for both neck/back/hip pain (−1.99 vs −0.18) and mBASDAI (−2.09 vs −0.59). Improvements in neck/back/hip pain and fatigue appeared numerically greater in HLA-B27+ than HLA-B27– patients; those for other domains were generally consistent. Greater proportions of ustekinumab versus placebo-treated patients achieved ASDAS clinically important improvement at Week 24 (decrease ≥ 1.1; 49.6% vs 12.7%; nominal p<0.05).ConclusionsImprovements in BASDAI neck/back/hip pain and mBASDAI among ustekinumab-treated, TNFi-naïve, PsA patients with PA-PRS were clinically meaningful and consistent across assessment tools. Numerically greater improvements in neck/back/hip pain in HLA-B27+ than HLA-B27– patients, noted in the context of similar overall mBASDAI improvements between the subgroups, suggest ustekinumab may improve disease activity in TNFi-naïve PsA patients likely to exhibit axial disease.Clinical trial registration numbersPSUMMIT 1, NCT01009086; PSUMMIT 2, NCT01077362.

ObjectiveThe objective was to investigate the short-term risk of major adverse cardiovascular events (MACEs) or congestive heart failure (CHF) in patients with psoriatic arthritis (PsA) or psoriasis initiating a biological therapy.MethodsScreening for the study was carried out using MEDLINE, Cochrane and Embase, from the inception of the database to December 2017. Randomised controlled trials (RCTs) of anti-tumour necrosis factor (TNF), anti-interleukin (IL)12/23, anti-IL23 and anti-IL17 agents for the treatment of PsA or psoriasis were included. Two investigators independently extracted MACEs or CHF data reported during the placebo-controlled phase. The primary outcome measures were the incidence of MACEs or CHF.ResultsOf 753 references screened, 62 articles were selected, and 12 articles were added by manual searches. Accordingly 77 RCTs were included in the meta-analysis (MA) (10 174 patient-years (P-Y)). No significant difference was observed in MACE incidences in patients receiving anti-TNF, anti-IL12/23, anti-IL23 or anti-IL17 agents in comparison to the placebo. However, 10 MACEs were observed in the anti-IL12/23 group (1150 P-Y) compared with 1 in the placebo group (652 P-Y), with 0.01 −0.00 to 0.02 event/P-Y risk difference, which is not statistically significant. This trend was not observed in the anti-IL23 group. No significant difference was observed in CHF incidence in patients receiving biological agents in comparison to placebo.ConclusionThis MA of 77 RCTs did not reveal any significant change in the short-term risk of MACE or CHF in patients with PsA or psoriasis initiating a biological therapy.