Claudia Pena Rossi

Atacicept, a recombinant fusion protein containing the extracellular, ligand-binding portion of the transmembrane activator and calcium modulator and cyclophilin-ligand interactor receptor, and the Fc portion of human immunoglobulin (Ig) G, is designed to block the activity of B-lymphocyte stimulator and a proliferation-inducing ligand, and may have utility as a treatment for B-cell-mediated diseases, such as systemic lupus erythematosus (SLE). This Phase Ib study investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of intravenous (i.v.) atacicept in patients with mild-to-moderate SLE. Patients (n = 24) were randomised (5:1) to receive atacicept (single dose: 3, 9 or 18 mg/kg; or multiple dose: 2 x 9 mg/kg) or matching placebo. Patients were followed for 6 weeks after dosing (9 weeks in the 2 x 9 mg/kg cohort). Local tolerability of atacicept was comparable with that of placebo, with only mild injection-site reactions reported with atacicept. Atacicept i.v. was generally well tolerated, both systemically and locally, in patients with mild-to-moderate SLE. Atacicept displayed non-linear PK, which was predictable across doses and between single and repeat doses. The biological activity of atacicept was demonstrated by its marked effect in reducing B-cells and Ig levels in patients with SLE. This supports the utility of this therapeutic approach in the treatment of autoimmune diseases, such as SLE.

Crohn's disease (CD) and multiple sclerosis (MS) share common pathogenic processes. Interferon (IFN) beta-1a is effective and generally well tolerated in patients with MS and has been shown to down-regulate the expression of interleukin-12, a cytokine that is thought to be involved in mucosal degeneration in CD. IFN beta-1a therefore offers promise as a treatment for CD.

Summary: Background Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro‐ and anti‐inflammatory cytokines. Interferon (IFN)‐β‐1a has potent immunoregulatory properties, including stimulation of host defence mechanisms and thus represents a potential treatment.Aim To extend pilot data and identify a suitable dose of IFN‐β‐1a to achieve endoscopically confirmed remission (ECR) in patients with moderately active UC and to evaluate safety.Methods In this multicentre, double‐blind, placebo‐controlled trial, adults with moderately active UC were randomized to IFN‐β‐1a 44 or 66 μg, or placebo, subcutaneously three times weekly for 8 weeks, with a 4‐week follow‐up.Results Endoscopically‐confirmed remission was observed in 23.4% [95% confidence interval (CI): 13.8–35.7] of placebo patients, 29.2% (95% CI: 18.6–41.8) of the IFN‐β‐1a 44 μg group and 20.0% (95% CI: 11.1–31.8) of the 66 μg group (P = 0.45). Improvements with IFN‐β‐1a 44 μg were greater than with placebo for most secondary efficacy outcomes, although significance was not achieved. Placebo response rates were higher than expected from previous trials. Adverse events were similar to the known safety profile of IFN treatment.Conclusions Interferon‐β‐1a was generally well tolerated at the doses tested, but a significant therapeutic benefit in patients with UC was not observed.