Lupus trials bring good news in 2020

Multiple positive lupus studies have been a bright spot in an otherwise dark year, according to a panel of experts summing up the presentations delivered at ACR Convergence 2020.

Highlights from the meeting were the  including a phase 2 RCT of iberdomide – a cereblon E3 ligase modulator with immunostimulatory activity – in active SLE.

The study, presented by Professor Joan Merrill of the University of Oklahoma, randomised 288 patients to one of three doses of iberdomide (0.15 mg, 0.3 mg, 0.45 mg QD) or placebo for 24 weeks.

The study found 54.3% of patients in the 0.45 mg dose of iberdomide met the primary end point of a SRI-4 response compared to 34.9% of controls (p=0.011).

Response rates in the groups receiving iberdomide at 0.15 mg and 0.3 mg were 47.6% and 40.2% respectively – higher than the controls but the treatment difference was not statistically different.

Professor Merrill, Director of Clinical Projects in the Arthritis & Clinical Immunology Program at the Oklahoma Medical Research Foundation, said the difference in response to iberdomide compared to placebo was evident at week 16 and continued.

“Elevated expression of the Aiolos gene and the type 1 interferon gene signature was strongly associated with the response to iberdomide,” she said.

Multiple secondary endpoints such as SRI-4 in patients with baseline SLEDAI 2K ≥10, SRI-4 in patients with steroid reduction, SLEDAI 2K ≥4 point improvement from baseline, and resolution of SLEDAI 2K arthritis or rash all favoured iberdomide 0.45 mg.

“Adverse events were more common in the iberdomide-treated patients and the most common adverse events were those reported for other lupus trials,” she said.

These included UTI, URTI, neutropenia, influenza, nasopharyngitis, leukopenia, diarrhoea and sinusitis. Rates of infections, neutropenia and rash were dose-dependent. The only death recorded was a PE in the control group.

Dr Merrill concluded the drug was well tolerated with an acceptable safety profile.

And the fact that the efficacy of the drug was enriched in two biomarker-defined populations – high expression of the Aiolos gene and a type 1 interferon signature – provided an opportunity for precision medicine, she added.

The trial was funded by Bristol Myers Squibb.

Monoclonal antibody improves skin in lupus

Also mentioned in the meeting highlights was a lupus study presented by Dr Victoria Werth, a dermatologist from the University of Pennsylvania, and co-authored by Australian rheumatologist Professor Eric Morand from Monash University, Melbourne.

The study, comprising pooled data from the phase 3 studies TULIP-1 and TULIP-2, further assessed the effect of anifrolumab on skin disease in active SLE.

The studies previously found anifrolumab resulted in treatment differences ≥17% versus placebo for achieving ≥50% CLASI-A reduction at week 12.

Dr Werth said that, in the combined group of more than 800 patients, 46% of patients treated with anifrolumab 300mg had a ≥50% CLASI-A reduction at week 12 compared to 24.9% of controls.

As well as the greater CLASI-A response at early time points, anifrolumab improved the time to onset of a sustained CLASI-A response.

Anifrolumab also resulted in greater response rates regardless of baseline cutaneous disease or response thresholds.

“Rapid and durable CLASI-A responses support the potential of anifrolumab to reduce skin disease activity irrespective of baseline cutaneous disease activity in patients with moderate to severe SLE,” she concluded.

The TULIP studies were funded by AstraZeneca.

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