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Objective Patient‐reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician‐derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated. Methods Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross‐validated error, comparing different ML approaches using both training and test data. Results A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient‐Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%. Conclusion ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real‐world evidence generation in the common circumstance when physician‐derived disease activity data are not available yet PRO measures are.

Objective To evaluate whether intravenous (IV) golimumab produces improvements in skin and nail symptoms that are concomitant with improvements in quality of life (QoL) and joint symptoms in patients with psoriatic arthritis. Methods Patients were randomized to either IV golimumab 2 mg/kg at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo at weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at weeks 24, 28, and then q8w through week 52. Assessments included Psoriasis Area and Severity Index (PASI), modified Nail Psoriasis Severity Index (mNAPSI), Dermatology Life Quality Index (DLQI), and American College of Rheumatology (ACR) rheumatoid arthritis response criteria. Results Through week 24, achievement of PASI 75/90/100 responses (P ≤ .0098) and mean improvements in mNAPSI (−11.4 vs −3.7; P < .0001) and DLQI (−9.8 vs −2.9; P < .0001) were significantly greater with golimumab versus placebo. Responses were maintained in patients treated with golimumab through week 52. In placebo‐crossover patients, increases in the proportion of patients achieving PASI 75/90/100 responses were observed from weeks 24 to 52, and mean improvements in mNAPSI (from −3.7 to −12.9) and DLQI (from −2.9 to −7.8) increased from weeks 24 to 52. Simultaneous achievement of PASI and DLQI responses, PASI and ACR responses, and mNAPSI and DLQI responses were also observed. Similar responses were observed for all assessments regardless of concomitant methotrexate use. Conclusion Improvements in skin and nail psoriasis symptoms with IV golimumab in patients with psoriatic arthritis were concomitant with improvements in QoL and arthritis disease activity through 1 year.

Abstract Background In the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment. Methods In this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2 mg/kg (N = 241; week 0, week 4, every 8 weeks [q8w]) or placebo (N = 239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed. Results Across indices, golimumab-treated patients demonstrated less radiographic progression than placebo-treated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were − 0.83 vs. 0.91, respectively, in patients achieving MDA and − 0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placebo-randomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab- vs. placebo→golimumab-treated patients achieving MDA were − 1.16 vs. 1.19, respectively) and regardless of whether low disease activity was achieved (0.03 vs. 1.50, respectively, in those not achieving MDA). Consistent patterns were observed for disease activity assessed using VLDA, PASDAS, DAPsA, and CDAI composite endpoints. Conclusions The extent of structural damage inhibition afforded by up to 1 year of intravenous golimumab treatment paralleled levels of PsA activity, with greater progression of structural damage observed in patients with sustained higher disease activity. Among patients not achieving low levels of disease activity across several composite indices, golimumab-randomized patients appeared to exhibit far less progression of structural damage than placebo-randomized PsA patients, illustrating a potential disconnect between responses, wherein golimumab can inhibit structural damage independent of clinical effect. Trial registration ClinicalTrials.gov. NCT02181673 . Registered 04 July 2014.

Abstract Background Patients with psoriatic arthritis (PsA) have increased risk of adverse events, including serious infections (SI), compared with psoriasis patients. Methods Patients eligible for, or receiving conventional systemic and biologic agents for psoriasis were followed prospectively using PSOLAR. Cohorts included: ustekinumab, tumor necrosis factor (TNF) inhibitors; infliximab; etanercept; adalimumab; non-biologic/methotrexate (MTX) (reference group); and non-biologic/non-MTX. Multivariate analyses using Cox hazard regression were used to identify factors associated with time to first SI. Rates of SI in PSOLAR psoriasis patients with self-reported PsA and possible risks with biologic therapy were evaluated. Results PSOLAR enrolled 4315 psoriasis patients with self-reported PsA. The overall population (N = 2401) included patients (n): 628 ustekinumab; 1413 TNF inhibitors; 258 infliximab; 481 etanercept; 674 adalimumab; 54 other biologics, 98 non-biologic/MTX; 208 non-biologic/non-MTX. Overall, 138 SI were reported with incidence rates per 100 patient-years as follows: a) ustekinumab: 1.00; b) TNF inhibitors: 2.22; c) infliximab: 2.12; d) etanercept: 2.58; e) adalimumab: 1.99; f) non-biologic/MTX: 3.01; g) and non-biologic/non-MTX: 2.31. Age, time-dependent disease activity Physician’s Global Assessment (PGA) of 4, 5, history of infection, and diabetes were associated with increased risk for SI (p

Abstract Objective To evaluate the safety and efficacy of intravenous golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) aged

Background The 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.Methods Patients 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.Results The 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

Abstract Background To evaluate demographics, family history, and previous medication use at enrollment in a subset of psoriasis patients with self-reported psoriatic arthritis (PsA) enrolled in Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods PSOLAR is an international, prospective, longitudinal, disease-based registry that collects data in patients receiving, or are eligible to receive, systemic or biologic treatments for psoriasis. Baseline demographic, disease characteristics, medical history, and prior medication use at enrollment were evaluated in PSOLAR psoriasis patients self-reporting PsA (n = 4315); a subset of which had their diagnosis of PsA established by a healthcare provider (HCP; n = 1719); patients with psoriasis only (n = 7775); and the overall PSOLAR population (n = 12,090). Results At enrollment, demographic characteristics were distinct between psoriasis patients self-reporting PsA and psoriasis only patients. Of the patients with psoriasis self-reporting PsA, 44.4% had cardiovascular disease (CVD), 26.3% had psychiatric illness, and 3.2% had inflammatory bowel disease (IBD), with each more prevalent than among patients with psoriasis only (p

To evaluate the safety, efficacy, and pharmacokinetics of 50 mg etanercept administered subcutaneously once weekly in adult patients with active rheumatoid arthritis (RA). Four hundred twenty RA patients were randomized to receive, in a blinded manner, the study drug for up to 16 weeks: 214 patients received 50 mg etanercept once weekly, 153 received 25 mg etanercept twice weekly, and 53 received placebo for 8 weeks followed by 25 mg etanercept twice weekly for 8 weeks. Efficacy and safety were assessed at weeks 8 and 16. Pharmacokinetic analyses were performed on serum samples from patients at selected study sites. The primary efficacy end point was achievement of the American College of Rheumatology (ACR) 20% improvement criteria (ACR20 response) at week 8. An ACR20 response was achieved at week 8 by 50% of the patients receiving 50 mg etanercept once weekly, by 49% of the patients receiving 25 mg etanercept twice weekly, and by 19% of the patients in the placebo group (P ≤ 0.0001 for each etanercept group versus placebo). Similarly, achievement of the ACR50 response was attained by 18% of patients in each of the 2 etanercept groups, compared with 6% of patients in the placebo group (P < 0.03 for each comparison). Pharmacokinetics of the 2 etanercept regimens were similar at steady state. No clinically significant differences in efficacy or safety were observed between the 2 etanercept groups. Safety, efficacy, and pharmacokinetics were comparable between the 2 etanercept dosing regimens. Thus, comparable clinical outcomes are to be expected when patients are treated with etanercept administered either as 50 mg once weekly or as 25 mg twice weekly. [ABSTRACT FROM AUTHOR]