This is a repository copy of Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial.

Objective. Guselkumab, a human monoclonal antibody specific to interleukin-23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER-2 trial in biologic-naive patients with psoriatic arthritis (PsA). Here we report 1-year DISCOVER-2 findings. Methods. Adults with active PsA (≥5 swollen and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized. Results. Of 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a ≥20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health-related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0-24 (4 of 493 [0.8%]) to weeks 24-52 (3 of 493 [0.6%]) among guselkumabrandomized patients. No patient developed an opportunistic infection or died. Conclusion. In biologic-naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk-benefit profile through week 52.

ObjectiveEvaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year.MethodsAdults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab 100 mg Q4W at Week24 (PBO→Q4W) through Week48. Clinical efficacy through Week52 (employing non-responder imputation) and adverse events (AEs) through Week60 were evaluated.ResultsOf 381 treated patients, 90% completed the study. Numerical increases in the proportions of patients achieving ≥20% improvement in ACR criteria (ACR20) were observed post-Week24, reaching 73% (94/128) and 60% (76/127) for Q4W-randomised and Q8W-randomised patients, respectively, by Week52. Proportions of patients achieving ACR50/ACR70/skin responses and minimal/very low disease activity were maintained, as were improvements in physical function and health-related quality of life, through Week52 in guselkumab-randomised patients. Response to guselkumab was maintained in both TNFi-naïve and TNFi-experienced patients. Serious AEs and serious infections occurred in similar proportions of guselkumab Q4W-randomised (3% and 0%) and Q8W-randomised (6% and 2%) patients through Week60, with no new safety concerns versus observations through Week24. No guselkumab-treated patient and two patients receiving placebo died; no study participant developed opportunistic infection or inflammatory bowel disease.ConclusionGuselkumab provided sustained improvement across multiple clinical manifestations of PsA, maintaining a favourable benefit-risk profile, through 1 year regardless of prior TNFi exposure.

Objectives: Contrast-induced acute kidney injury (CI-AKI) is defined as either a 25% increase in or an absolute elevation in serum creatinine (SCr) of 0.5 mg/dL, 48 to 72 hours after parenteral contrast exposure. The objective of this study was to compare the incidence and complications of AKI between patients exposed and those unexposed to intravenous (IV) contrast.Methods: This was a retrospective cohort study using the electronic medical record of adult patients (>18 years) with and without contrast-enhanced abdominal or chest computed tomography (CT) between May 2008 and April 2009. Inclusion criteria were emergency department (ED) patients with normal renal function who received either a contrast-enhanced abdominal or a contrast-enhanced chest CT, compared to those unexposed to IV contrast, with a repeat SCr within 48 to 72 hours. Exclusion criteria were contrast exposure within 7 days before the index visit. CI-AKI in the contrast-exposed group and AKI in the contrast-unexposed group were defined by the same changes in SCr 48 to 72 hours after contrast or ED admission. Data were described by proportions or medians with 95% confidence intervals (CIs) or interquartile ranges (IQR; 25% to 75%). Group comparisons were by Mann-Whitney U or Fisher's exact test (a = 0.05, two tails).Results: The contrast-exposed (n = 773) and contrast-unexposed (n = 2,956) patients were evenly matched for initial demographic, renal, and metabolic parameters. The incidence of CI-AKI/AKI was significantly higher for the patients unexposed versus exposed to contrast (8.96% vs. 5.69%, p = 0.003). There was no significant difference in mortality rates between contrast-exposed and unexposed patients (9.09% vs. 6.79%, p = 0.533). Conclusions:The definition of CI-AKI for ED patients with normal renal function may not represent a true clinical entity and the definition warrants revision.