An Evidence-Based Drug Update & Guidance for Rheumatologists

Dr. Curtis highlighted a curiosity of the trial that stood out to him. “Remember what this drug does: It’s a monoclonal antibody to type I IFN receptor sub-unit 1,” he said. “So wouldn’t you expect the British Isles Lupus Activity Group [BILAG] Based Composite Lupus Assessment [BICLA] response in people with a high IFN gene signature to be even better than for [those with a low IFN gene signature]? Well, it wasn’t. I find it curious that what you’d think could be a stratifying biomarker in fact wasn’t stratifying. The response rate was just about as good for people without the signature.”

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He also pointed out the increased risk of herpes zoster with anifrolumab and stressed the importance of vaccination.

“The rate of herpes zoster was quite high [7.2%], but you expect that in any drug that meaningfully affects the IFN pathway,” Dr. Curtis said. “So in fact, this rate of zoster would be pretty comparable to a patient with RA on a Janus kinase inhibitor and 10 mg of prednisone daily—or maybe even a bit more. Zoster vaccination will be quite critical for the people you’re putting on this [treatment].”

When asked which type of SLE patient he would prescribe anifrolumab for, Dr. Curtis said, “Patient selection is obviously critical. Remember, this wasn’t a drug targeted for severe lupus nephritis or neuro-psychiatric SLE, and the effect on joint disease wasn’t overwhelming [but the trial wasn’t powered for that and not all patients had joint disease]. I think typical SLE manifestations with the exclusion of those three is probably where I would position it.”

Voclosporin

Voclosporin is a calcineurin inhibitor (CNI) now approved in combination with a regimen of background immunosuppressive therapy for the treatment of adult patients with active lupus nephritis. Unlike older CNIs (e.g., tacrolimus), voclosporin doesn’t require drug level monitoring.

“[Trial] inclusion criteria are important when we’re thinking about when to use this drug,” said Dr. Curtis.

Patients studied had lupus nephritis class III, IV or V confirmed with renal biopsy within the last two years, relatively preserved renal function, with an estimated glomerular filtration rate (eGFR) greater than 45 mL per minute, and urine protein-creatinine ratio of 1.5 mL/mg or more (e.g., 2 mL/mg for those with pure lupus nephritis class V) by first morning urine void.²

Voclosporin was added to 1,000 mg of mycophenolate mofetil (MMF) given twice daily with a rapid prednisone taper from 20–25 mg daily, to 2.5 mg daily over 16 weeks. The primary outcome was complete renal response, which was 41% in the voclosporin arm and 23% in placebo “despite a really rapid and aggressive prednisone taper.”