Peter Ryan

LY2439821, a humanized anti–interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I randomized, double-blind, placebo-controlled, proof-of-concept study

OBJECTIVE We undertook this study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized anti-interleukin-17 (anti-IL-17) monoclonal antibody, in a first in-human trial in rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic drugs (DMARDs). METHODS This randomized, double-blind, placebo-controlled study consisted of 2 parts. In part A, 20 patients received 1 intravenous (IV) dose of LY2439821 (0.06, 0.2, 0.6, or 2.0 mg/kg, escalating) or placebo followed by 8 weeks of evaluation. End points included safety, tolerability, and pharmacokinetics. In part B, 77 patients received 1 IV dose of LY2439821 (0.2, 0.6, or 2.0 mg/kg) or placebo every 2 weeks for a total of 5 doses, with a total evaluation period of 16 weeks. End points included safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy (Disease Activity Score in 28 joints [DAS28] and percentages of patients meeting American College of Rheumatology 20%, 50%, or 70% improvement criteria [achieving an ACR20, ACR50, or ACR70 response]). The primary efficacy end point was the DAS28 at week 10. RESULTS Baseline characteristics were similar across all groups. Changes in the DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821-combined groups (-2.3, -2.4, and -2.3, respectively) than in the placebo group (-1.7) at week 10 (P < or = 0.05), and these differences were significant as early as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points. There was no apparent dose-response relationship in treatment-emergent adverse events. CONCLUSION LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted. This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA.

Australian Comparative Outcome Trial of Angiotensin-Converting Enzyme Inhibitor And Diuretic-Based Treatment of Hypertension in the Elderly (ANBP2): Objectives and Protocol

1. ANBP2 is a comparative outcome trial of angiotensin‐converting enzyme inhibitor‐ and diuretic‐based treatment of hypertension in the elderly using a prospective randomized open‐label design with blinding of endpoint assessments.

Malignancy‐associated remission of systemic lupus erythematosus maintained by autologous peripheral blood stem cell transplantation

Many investigators worldwide are currently exploring the role of peripheral blood stem cell transplantation (PBSCT) in managing autoimmune diseases. We report the case of a woman with systemic lupus erythematosus (SLE) with mucocutaneous and renal involvement, who underwent PBSCT for stage IVB Hodgkins disease. Following the development of the lymphoma, she has had a prolonged clinical and serologic remission of the SLE. The potential effects of lymphoproliferative disorders and PBSCT on the course of SLE are considered.

Post–cardiac transplantation gout: incidence of therapeutic complications

OBJECTIVE To study the clinical impact of gout treatment following cardiac transplantation. METHODS We performed an audit of all cardiac transplant recipients of the Alfred Hospital before August 1998 who lived in Victoria. RESULTS We studied 225 patients (81% men), with a mean post-transplant follow-up of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring post-transplantation. Twenty-three patients developed gout de novo. Of the 24 patients who received allopurinol, 6 developed pancytopenia and required hospitalization. Fourteen received a change in immunosuppression: in 5 patients following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two patients received colchicine; 5 developed neuromyopathy. Impaired renal function, diuretic use, and hypertension were more common in this sub-group. Non-steroidal anti-inflammatory agents, used in 16 patients, caused serious complications in 1 patient (life-threatening peptic ulceration and hemorrhage, precipitating dialysis-dependent chronic renal failure). CONCLUSIONS Cardiac transplant recipients, when treated for gout, are at high risk of therapeutic complications. Thus, gout treatment significantly affects care, health, and immunosuppression of these patients.

Mast cells as a target in the treatment of rheumatoid arthritis.

Abstract— Mast cells represent a unique cell population, which is involved in a number of immune responses in our body. Mast cells (MCs) release an array of potent pro-inflammatory mediators and cytokines upon activation that are either pre-stored in the granules or synthesised de novo. These mediators can make a substantial contribution to the initiation and perpetuation of the inflammatory processes. This review provides an insight for the potential role of MCs in rheumatoid arthritis (RA). The data on mast cell distribution in the rheumatoid joint along with the information obtained from in vitro experiments and observations in animal models suggest that these cells may be involved in RA. The encouraging results of MC inactivating therapy in animal models of arthritis indicate that MC stabilizers may prove beneficial as a supplementary therapy in RA.