Novel Psoriasis Therapies and Patient Outcomes, Part 2: Biologic Treatments
Biologic treatments have revolutionized the management of psoriasis and psoriatic arthritis (PsA). Anti–tumor necrosis factor (TNF) α monoclonal antibodies presently are approved by the US Food and Drug Administration (FDA) for treatment of these conditions. In this article, new therapies that target this pathway and other steps in the pathogenesis of psoriasis and PsA are discussed, including IL-12/IL-23, IL-17, T-cell activation in antigen-presenting cells, regulatory T cells, toll-like receptors, and granulocyte-macrophage colony-stimulating factor. This article is the second in a 3-part series on treatments presently in the pipeline for the management of psoriasis and PsA including topical agents, biologic treatments, and systemic therapies in phase 2 through phase 4 clinical trials as well as agents that are recently FDA approved. Pivotal clinical trials, mechanisms of action, patient outcomes, and pertinent safety information will be discussed for each new therapy. As our knowledge of the underlying pathogenesis of psoriasis and PsA deepens, it enables the development of more targeted therapies in the management of these conditions.
Practice Points
- Novel biologic treatments promise exciting new therapeutic avenues for psoriasis and psoriatic arthritis (PsA).
- Although biologics currently in use for treatment of psoriasis and PsA are in the form of tumor necrosis factor α inhibitors, other drugs in phase 2 through phase 4 clinical trials aim to target alternative pathways underlying the pathogenesis of these disorders, including IL-12/IL-23 inhibition, IL-17 inhibition, inhibition of T-cell activation in antigen-presenting cells, regulatory T-cell activation, toll-like receptor inhibition, and granulocyte-macrophage colony-stimulating factor inhibition.
- New approaches to the management of psoriasis and PsA offer patients hope for more targeted treatment regimens.
Inhibition of Toll-like Receptors 7, 8, and 9
IMO-8400
IMO-8400 (Idera Pharmaceuticals) is unique in that it treats psoriasis by targeting toll-like receptors (TLRs) 7, 8, and 9.37 In phase 1 studies, IMO-8400 was well tolerated when administered to a maximum of 0.6 mg/kg.38 An 18-week, phase 2, randomized, double-blind, placebo-controlled, dose-ranging study evaluating the safety and tolerability of different dose levels—0.075 mg/kg, 0.15 mg/kg, and 0.3 mg/kg—of IMO-8400 versus placebo in patients with moderate to severe plaque psoriasis was completed, but the results were not available at the time of publication (NCT01899729).
Inhibition of Granulocyte-Macrophage Colony-Stimulating Factor
Namilumab (MT203)
Namilumab (formerly known as MT203)(Takeda Pharmaceutical Company Limited) is a granulocyte-macrophage colony-stimulating factor inhibitor. At the time of publication, participants were actively being recruited for a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-finding and proof-of-concept study to assess the efficacy, safety, and tolerability of namilumab at 4 different SC doses—300 mg, 160 mg, 100 mg, and 40 mg at baseline with half the dose on days 15, 43, and 71 for each of the 4 treatment arms—versus placebo in patients with moderate to severe chronic plaque psoriasis (NCT02129777).
Conclusion
Novel biologic treatments promise exciting new therapeutic avenues for psoriasis and PsA. Although biologics currently are in use for treatment of psoriasis and PsA in the form of TNF-α inhibitors, other drugs currently in phase 2 through phase 4 clinical trials aim to target other pathways underlying the pathogenesis of psoriasis and PsA, including inhibition of the IL-12/IL-23 pathway; inhibition of the IL-17 pathway; inhibition of T-cell activation in antigen-presenting cells; activation of regulatory T cells; inhibition of TLR-7, TLR-8, and TLR-9; and inhibition of granulocyte-macrophage colony-stimulating factor. These novel therapies offer hope for more targeted treatment strategies for patients with psoriasis and/or PsA.
