Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3

The existing states of mercury and selenium in the blood and in soluble fractions of perfused rabbit liver and kidney were studied by gel filtration on Sephadex G-200 1 hr or 24 hr after intravenous injection of mercuric chloride and/or sodium selenite. Both mercury and selenium in the plasma and stroma-free hemolysate were found to exist in the high-molecular weight fraction following simultaneous injection of mercuric chloride and sodium selenite. Patterns in gel filtration of the plasma and the stroma-free hemolysate did not show any significant change between 1 hr and 24 hr after the administration. A similar tendency as described above was obtained with the liver-soluble fraction at 24 hr after injection of mercuric chloride and sodium selenite. A possible role of the high-molecular weight complex, which is quickly formed by the interaction of mercury and selenium in blood stream, in decreasing the acute renal toxicity of inorganic mercury is discussed.

Abstract Background/Aims It is useful to evaluate individual American College of Rheumatology (ACR) components in large trials for active psoriatic arthritis (PsA) because individual patient domains may influence treatment choice. SPIRIT-H2H showed superiority of ixekizumab (IXE) over adalimumab (ADA) in patients with PsA and inadequate response (IR) to conventional synthetic disease modifying antirheumatic drugs (csDMARDs). This analysis describes the effect of IXE and ADA on individual ACR components at week (Wk) 52, with and without concomitant methotrexate (MTX) and csDMARDs. Methods Patients from SPIRIT-H2H (NCT03151551, 52 Wk randomized multicenter study) who met Classification Criteria for Psoriatic Arthritis (CASPAR) (N = 566), were randomized (1:1, stratified by baseline concomitant csDMARDs and moderate-to-severe PsO) to IXE or ADA on-label PsA or PsO dosing. Patients were bDMARD-naïve with IR to csDMARDs, active PsA (≥3 tender joints [TJC] and ≥3 swollen joints [SJC]) and had psoriasis (PsO) ≥3% BSA (body surface area). Patient’s Global Assessment (PtGA) and Physicians Global Assessment (PGA), Health Assessment Questionnaire-Disability Index (HAQ-DI), and joint pain were assessed by visual analog scale, and TJC and SJC as well as C-reactive protein (CRP) were analyzed. All post-hoc analyses were performed on the intent-to-treat (ITT) population. Change from baseline (CFB) in individual ACR components was analyzed using an Analysis of Covariance (ANCOVA) model, for overall as well as with and without concomitant therapies (e.g., MTX or csDMARD). Least square mean (LSM) and standard error (SE) are presented. Missing data were imputed using modified baseline observation carried forward (mBOCF). Nine patients with active PsO and BSA≥3% were assessed as Psoriasis Area and Severity Index (PASI)=0 at baseline, a medical inconsistency that was resolved using medical judgment. These patients were considered PASI100 responders if PASI=0 and BSA=0 at post baseline visits. Results A total of 566 patients received either IXE (N = 283) or ADA (N = 283). Baseline values for individual ACR components were balanced between IXE and ADA. At Wk 52, IXE demonstrated efficacy across all individual ACR components in the ITT population, specifically in PGA, PtGA and Joint Pain; ADA also demonstrated numerical efficacy. Improvements from baseline for IXE were observed across ACR components, with or without MTX or csDMARD. The effect of MTX (with or without) was notably different between IXE and ADA in TJC68, PGA, Joint Pain, and PtGA. Conclusion In this analysis, there was improvement with IXE in all components of the ACR composite score at Wk 52, irrespective of MTX or csDMARD use (with or without). In the ITT population, IXE showed comparable efficacy to ADA at Wk 52 in all components of ACR, demonstrating improvement across musculoskeletal domains. These results may provide further confidence of the clinical benefits of ixekizumab across musculoskeletal domains in patients with PsA, regardless of MTX or csDMARD use. Disclosure A. Kiprianos: None. E. Husni: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, and UCB Pharma. S. Kamat: Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly and Company, and Exogen. K. Stenger: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. T. Holzkaemper: Shareholder/stock ownership; Eli Lilly and Company. C.C. Helt: Shareholder/stock ownership; Eli Lilly and Company. S. Park: Shareholder/stock ownership; Eli Lilly and Company. J.R. Lisse: Shareholder/stock ownership; Eli Lilly and Company. L. Idolazzi: Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly and Company, and Janssen.

An amendment to this paper has been published and can be accessed via the original article.

This study assessed if concomitant use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or corticosteroids altered the response or safety outcomes to baricitinib in rheumatoid arthritis (RA) patients.

Background Baricitinib (BARI), an oral JAK1/JAK2 inhibitor, is in development for patients (pts) with moderate to severe rheumatoid arthritis (RA).1,2 Objectives This post-hoc analysis of two phase 3 studies assessed whether concomitant use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) altered the response or safety outcomes to BARI in RA pts and evaluated the effect of concomitant corticosteroid use on the efficacy of BARI. Methods Pts with ≥6 swollen and tender joints and no prior biologic DMARD use were enrolled. In RA-BEAM (NCT01710358), methotrexate (MTX)-inadequate responder (IR) pts were randomised to PBO once daily (QD), BARI 4 mg QD, or adalimumab 40 mg biweekly.1 In RA-BUILD (NCT01710358), csDMARD-IR pts were randomised to placebo (PBO) or BARI (2 or 4 mg) QD.2 Pts continued background csDMARD (including MTX) therapy. This post-hoc analysis included the PBO (N=716) and BARI 4 mg (N=714) pts and assessed the number and type of concomitant csDMARDS and concurrent corticosteroid use. Results 71%, 21%, and 6% of PBO pts were taking MTX alone, MTX + ≥1 other csDMARD, and non-MTX csDMARDs, respectively; in BARI 4 mg pts, the rates were 74%, 18%, and 6%, respectively. Oral corticosteroids were used in 56% of PBO and 55% of BARI pts at baseline; pts continued use throughout the studies. The differences in clinical efficacy between BARI 4 mg and PBO at 12 weeks was similar regardless of the number or type of csDMARDs concomitantly used (Table) or the concomitant use of corticosteroids (data not shown). The rates of serious adverse events and discontinuation due to adverse events were comparable regardless of the number or type of csDMARDs used (Table) or corticosteroid use. ACR20/50/70=20%, 50%, and 70% improvement in American College of Rheumatology criteria; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; DAS28-ESR=Disease Activity Score 28-erythrocyte sedimentation rate; MTX=methotrexate; SDAI=Simple Disease Activity Index. Conclusions BARI has demonstrated clinical safety and efficacy in a wide range of pts, regardless of the number of concomitant csDMARDs or concomitant use of corticosteroids. References Taylor PC et al. Arthritis Rheumatol 2015;67(S10):3927–3928. Dougados M et al. Ann Rheum Dis 2017;76:88–95. Disclosure of Interest A. Kavanaugh Consultant for: Eli Lilly and Company, C. Helt Employee of: Eli Lilly and Company, D. Muram Employee of: Eli Lilly and Company, J. Alam Employee of: Eli Lilly and Company, V. Arora Employee of: Eli Lilly and Company, A. L. Pinto Correia Employee of: Eli Lilly and Company, I. de la Torre Employee of: Eli Lilly and Company, R. van Vollenhoven Grant/research support from: Abbvie, Amgen, BMS, GSK, Pfizer, Roche, UCB, Consultant for: Abbvie, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB, Vertex