Emerging IL-6 Inhibitors

Two emerging non-TNF biologics, sarilumab and sirukumab, have completed phase III development. Sarilumab is a fully human monoclonal antibody against IL-6Ra, whereas sirukumab is a human monoclonal antibody that targets IL-6 itself.1Decisions from the FDA regarding approval of these drugs are expected soon. Olokizumab is beginning phase III development, and clazakizumab has completed phase IIb testing.

The following list are of new drugs, many of which are yet to be available to patients at this time (June 2018). Speak to your rheumatologist to discuss the matter further.

Sirukumab

Unlike tocilizumab and sarilumab, sirukumab is a human monoclonal antibody that targets IL-6 rather than IL-6R. Clazakizumab (ALD518, BMS945429) The rates of serious adverse effects reported through week 24 with sirukumab 50 mg every 4 weeks, 2.7% with sirukumab 100 mg every 2 weeks, and 4.3% with adalimumab were minimal. No deaths have been reported in either study.

Olokizumab (CDP6038)

Among clazakizumab-treated patients, 12 serious infections were reported. This rate was comparable to that reported among adalimumab-treated patients and more than among patients who were treated with methotrexate monotherapy.

Emerging JAK Inhibitors Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs by Annals of the Rheumatic Diseases. Four oral JAK inhibitors are currently in late-stage development: baricitinib, ABT-494, filgotinib (GLPG0634), and peficitinib (ASP015K). Of these, baricitinib is the furthest along in development, having completed four phase III trials.

Baricitinib

The U.S. FDA has approved the 2 mg dose of baricitinib for the treatment of adults with moderately-to-severely active RA who have had an inadequate response to one or more TNF inhibitor therapies. Baricitinib may be used as monotherapy or in combination with MTX or other non-biologic DMARDs.

Upadacitinib (ABT-494)

Serious infections were observed in 1% of patients of who received placebo, 1% of patients who received baricitinib, and in less than 1% of those who received adalimumab.

Filgotinib (GLPG0634)

Early data showed rapid and persistent improvement of patient assessment of disease activity and pain, physical function, fatigue, and health-related quality of life.