‘Eclectic’, what a great word to describe the approaches to the development of drugs in systemic lupus erythematosus (SLE)! ‘Eclectic’ comes from a Greek verb meaning ‘to select’ and was originally applied to ancient philosophers who were not committed to any single system of philosophy; instead, these philosophers selected whichever doctrines pleased them from every school of thought.¹ Much like the ancient Greek philosophers, drug target selection in SLE has spanned many pathways. Although belimumab has been the sole drug approved to date via the traditional route of a randomised controlled trial, it’s just a matter of time before drugs targeting other molecules and pathways are granted approval for SLE and lupus nephritis.

The potential drug targets in SLE appear limitless, making decisions regarding resource allocation incredibly challenging. Should components of the innate or the adaptive immune system be targeted? Perhaps both? This presentation will review various strategies being pursued in order to inhibit key pathways in SLE. The emphasis will be on investigational agents in Phase I and Phase II programmes.^2–7

Learning Objectives

• Describe strategies for inhibiting the type I interferon pathway

• Discuss methods to target B and T cells

• Review approaches to down-regulate pro-inflammatory cytokines

References

1. Merriam-Webster Unabridgedaccessed June 19, 2020.

2. Furie R, Werth VP, Merola JF, et al. Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. J Clin Invest 2019;129(3):1359–71.

3. Furie R, Aroca G, Alvarez A, et al. A Phase II Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Obinutuzumab or Placebo in Combination with Mycophenolate Mofetil in Patients with Active Class III or IV Lupus Nephritis [abstract]. Arthritis Rheumatol 2019;71 (Suppl. 10).

4. Isenberg D, Furie R, Jones N, et al. Efficacy, Safety, and Pharmacodynamic Effects of the Bruton’s Tyrosine Kinase Inhibitor, Fenebrutinib (GDC-0853), in Moderate to Severe Systemic Lupus Erythematosus: Results of a Phase 2 Randomized Controlled Trial [abstract]. Arthritis Rheumatol 2019;71 (Suppl. 10).

5. Papp K, Gordon K, Thaçi D, et al. Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. N Engl J Med 2018;379(14):1313–21.

6. Furie R, Bruce I, Dörner T, et al. Efficacy and Safety of Dapirolizumab Pegol in Patients with Moderately to Severely Active Systemic Lupus Erythematosus: A Randomized, Placebo-Controlled Study [abstract]. Arthritis Rheumatol 2019;71 (Suppl. 10).

7. Basta F, Fasola F, Triantafyllias K, et al. Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New. Rheumatol Ther 2020 doi: 10.1007/s40744-020-00212-9 [published Online First: 2020/06/04].