Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study.

Objectives: Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX).

Methods: In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included.

Disruption of memory B-cell trafficking by belimumab in patients with systemic lupus erythematosus.

Objectives: Autoreactive memory B cells (MBCs) contribute to chronic and progressive courses in autoimmune diseases like SLE. The efficacy of belimumab (BEL), the first approved biologic treatment for SLE and LN, is generally attributed to depletion of activated naïve B cells and inhibition of B-cell activation. BEL's effect on MBCs is currently unexplained.

Evaluating disease control following belimumab treatment in patients with SLE enrolled in the US OBSErve study.

Objective: To characterise disease control and remission in patients with SLE receiving belimumab for up to 12 months in the real world.

Methods: This post hoc analysis (GSK Study 213502) used data from the US evaluation Of use of Belimumab in clinical practice SEttings (OBSErve) study (GSK Study 117295), an observational cohort study of adults with SLE initiating and continuing belimumab for ≥6 months. Data were collected every 6 months by physician chart review; details of disease activity using the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score were collected if routinely used by physicians.

Benzoxazolinone aryl sulfonamides as potent, selective Na1.7 inhibitors with in vivo efficacy in a preclinical pain model.

Studies on human genetics have suggested that inhibitors of the Na1.7 voltage-gated sodium channel hold considerable promise as therapies for the treatment of chronic pain syndromes. Herein, we report novel, peripherally-restricted benzoxazolinone aryl sulfonamides as potent Na1.

Discovery of a pharmacologically active antagonist of the two-pore-domain potassium channel K2P9.1 (TASK-3).

TWIK-related acid-sensitive K(+) (K(2P) 9.1, TASK-3) ion channels have the capacity to regulate the activity of neuronal pathways by influencing the resting membrane potential of neurons on which they are expressed. The central nervous system (CNS) expression of these channels suggests potential roles in neurologic disorders, and it is believed that the development of TASK-3 antagonists could lead to the therapeutic treatment of a number of neurological conditions.

In vitro characterization of T-type calcium channel antagonist TTA-A2 and in vivo effects on arousal in mice.

T-type calcium channels have been implicated in many behaviorally important neurophysiological processes, and altered channel activity has been linked to the pathophysiology of neurological disorders such as insomnia, epilepsy, Parkinson's disease, depression, schizophrenia, and pain. We have previously identified a number of potent and selective T-type channel antagonists (Barrow et al., 2007; Shipe et al.