SLE: Closer to Treatment Breakthroughs

Finally, there is hope in SLE treatment. 

Lupus nephritis likely needs two drugs to improve remission.

There is a lack of full remission in lupus nephritis with MMF or cyclopshosphamide with steroids. In an earlier RCT, tacrilomus was added to mycophenylate mofetil, which was superior to cyclophosphamide monotherapy but MMF monotherapy was not compared (Liu Z. Ann Intern Med 2015:162:18-26). Voclosporin is a novel calcineurin inhibitor. A multisite study enrolled active lupus nephritis patients and randomized them to treatment with 2 g/d mycophenolate mofetil alone or with the addition of low- or high-dose voclosporin (Dooley #L5). Time to complete remission was better with the addition of voclosporin to MMF compared to MMF alone. Maybe it is time to change our treatment paradigm to two drugs instead of using MMF alone.

Anifrolumab Phase IIb RCT in SLE

A positive trial in patients with active SLE that compared anifrolumab 300 or 1000 mg to placebo every 4 weeks for 48 weeks was previously reported at EULAR 2016.  Anifrolumab was shown to be better than placebo for rash, alopecia and arthritis (Merrill JT, #2009), with 300 mg anifrolumab in IFN-high patients showing the best response.

This study offers some mechanistic insights to help understand the results. SLE patients with more severe disease activity (SLEDAI≥10) had type I IFN, which may be involved in cell migration into the peripheral tissues from the blood (Stephens G. #760). Neutralization of type I IFN with anifrolumab promoted immigration and/or prevented emigration of potentially pathologic immune cells between the tissues and the blood.

Rituximab in SLE

Several cases of rituximab response in SLE were reported at this ACR meeting. However, access for this indication is difficult due to the previously negative renal and non-renal RCTs in SLE with rituximab.

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