Clinical efficacy, radiographic and safety findings through 2 years of golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of the randomised, placebo-controlled GO-REVEAL study

Objectives: To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis (PsA).<p></p> 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).<p></p> 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.<p></p> 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.<p></p&gt

Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab

<p>Objective To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA).</p> <p>Methods GO–REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14.</p> <p>Results Serum levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16, myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen, intercellular adhesion molecule 1 and macrophage inflammatory protein 1α) at baseline or week 4 were strongly associated with American College of Rheumatology 20% improvement (ACR20) response and/or disease activity score in 28 joints (DAS28) at week 14. A smaller subset of proteins was significantly associated with a 75% improvement in the psoriasis area and severity index score (PASI75) at week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic transaminase, and tumour necrosis factor α). Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures, and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone.</p> <p>Conclusions This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75 responses following golimumab treatment.</p&gt

Assessing structural damage progression in psoriatic arthritis and its role as an outcome in research

Psoriatic arthritis (PsA) is an immune-mediated, clinically heterogeneous disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis of the skin and nails. Persistent articular inflammation in patients with PsA can lead to structural damage, which can result in reduced physical function and quality of life. Structural damage can occur rapidly, and irreversible joint damage may be observed if patients are not treated promptly and appropriately. Therefore, evaluating therapeutic agents for their ability to inhibit structural progression has become increasingly important, with radiographic progression becoming a key efficacy outcome in clinical trials in PsA. Here, we review how structural damage and progression are assessed in clinical trials and the use of radiographic progression as a study outcome. We also discuss possible limitations in the current assessment of radiographic progression as well as areas of research that may improve the assessment of structural damage in clinical trials of PsA.Pathophysiology and treatment of rheumatic disease

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data

Background: Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). Methods: The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. Results: A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. Conclusions: Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions

Early Disease Activity or Clinical Response as Predictors of Long-Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis

Pathophysiology and treatment of rheumatic disease

Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1

Pathophysiology and treatment of rheumatic disease

Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through two years: results from a phase III, randomized, double-blind, placebo-controlled study conducted in biologic-naive patients with active Psoriatic Arthritis

Objective To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial. Methods In the DISCOVER-2 trial, patients with active PsA (>= 5 swollen joints and >= 5 tender joints; C-reactive protein level >= 0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24. Efficacy assessments included American College of Rheumatology >= 20%/50%/70% improvement criteria (ACR20/50/70), Investigator's Global Assessment (IGA) of psoriasis score of 0 (indicating complete skin clearance), resolution of enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score), and changes in the Sharp/van der Heijde modified radiographic scores for PsA. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112. Results Of the 739 randomized and treated patients, 652 (88%) completed treatment through week 100. Across groups of guselkumab-treated patients (including those in the placebo-guselkumab crossover group), the following findings at week 100 indicated that amelioration of arthritis signs/symptoms and extraarticular manifestations was durable through 2 years: ACR20 response (68-76%), ACR50 response (48-56%), ACR70 response (30-36%), IGA score of 0 (55-67%), enthesitis resolution (62-70%), and dactylitis resolution (72-83%). Mean changes in the Sharp/van der Heijde modified score for PsA from weeks 52 to week 100 (range 0.13-0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100. Through week 112, 8% (5.8 per 100 patient-years) and 3% (1.9 per 100 patient-years) of the 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; 1 death occurred (road traffic accident). Conclusion In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2 years.Pathophysiology and treatment of rheumatic disease

Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA

Pathophysiology and treatment of rheumatic disease