Ioannis Parodis, MD


August 10, 2015

In This Article

Lupus: New Definitions, Pipeline Agents, and New Data

In the field of SLE, van Vollenhoven and colleagues[26] presented results from an international multidisciplinary expert panel for the Definition of Remission in SLE (DORIS) project, aiming to achieve consensus on definitions. This initiative underscored the need for definitions for use in both clinical practice and research, and it paves the way for similar future endeavors in rheumatology.

Mixed efficacy results were presented by Isenberg and colleagues[27] from two phase 3, multicenter, randomized, placebo-controlled trials of tabalumab, a human IgG4 monoclonal antibody that binds and neutralizes membrane and soluble BLyS (ie, a mechanism consistent with BLyS inhibition). The primary endpoint, which was response according to the SLE Responder Index 5, was met in one of the two trials in patients receiving tabalumab every second week, but not in patients receiving tabalumab every fourth week. Increases in C3 and C4 levels and reductions of total B-cell and immunoglobulin counts and anti–double-stranded DNA were observed. The safety profile of tabalumab was similar to that of placebo across both trials.

PF-04236921 is a fully human monoclonal antibody that binds to circulating IL-6 and neutralizes its activity. Smolen and colleagues[28] evaluated the efficacy, safety and tolerability of this antibody in 183 patients with active SLE given 10 mg, 50 mg, or 200 mg of the drug or placebo subcutaneously every 8 weeks. An efficacy "signal" was seen at week 24: Patients receiving the anti–IL-6 monoclonal antibody showed lower rates of severe flares. The safety profile of the drug was acceptable for the lower doses of 10 mg and 50 mg, but the 200-mg dose had to be terminated owing to safety concerns. In the 10-mg group, patients with higher disease activity (SLE Disease Activity Index ≥ 10), detectable anti–double-stranded DNA, low complement levels, or prednisone dose > 7.5 mg/day showed better outcomes across several key parameters. Larger trials will help clarify the safety and efficacy of this agent for treating SLE.

New data were presented on belimumab, with Bruce and colleagues[29] reporting data on long-term organ damage and safety after 5 years of treatment with belimumab plus standard-of-care therapy in patients with SLE. They found a low incidence of organ damage accrual and clinically manageable rates of adverse events. Patients with preexisting organ damage had similar rates of damage accrual compared with patients with no damage at baseline. Because existing organ damage is a known risk factor for future damage accrual, these results suggest that belimumab may have protective effects on organ damage.


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