Positive clinical advances in systemic lupus erythematosus

The results of two studies presented at EULAR 2018 demonstrate exciting advances for individuals suffering from systemic lupus erythematosus (SLE).

The first is a phase 2 clinical study of a promising oral treatment, baricitinib. The second demonstrates the effective use of the shingles vaccine in SLE patients who are particularly prone to this infection.

“Novel therapeutic strategies are needed for SLE, which causes significant morbidity and mortality, and so we are delighted to see the positive results from the phase 2 trial of baricitinib,” said Prof Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR. “In addition, we welcome data on the vaccination of SLE patients against shingles, as currently, there is considerable clinical uncertainty around this issue.”

Treatment of SLE traditionally involves non-specific anti-inflammatory or immunosuppressive medications. However, this approach is ineffective in many patients and can be associated with many undesirable side-effects.

In the new phase 2 study, SLE patients taking baricitinib (an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 approved for the treatment of rheumatoid arthritis in Europe and Japan) had a significant improvement in several clinical outcomes compared to placebo.

This study included 314 patients with SLE receiving stable background therapy who were randomised 1:1:1 to placebo, baricitinib 2mg or 4mg once daily. Patients on baricitinib 4mg achieved significant resolution of arthritis or rash (Systemic Lupus Erythematosus Disease Activity Index 2000, SLEDAI-2K) compared with placebo (67 per cent vs 53 per cent, p<0.05), which was the primary end-point of the study. Patients on baricitinib 4mg also achieved a significantly greater SLE Responder Index (SRI-4) response (64 per cent vs 48 per cent, p<0.05), as well as flare reduction (SELENA-SLEDAI Flare Index), improvement in Lupus Low Disease Activity State (LLDAS) and reduced tender joint count. Rates of adverse events leading to treatment discontinuation and serious adverse events were higher for both baricitinib doses compared to placebo. There were no deaths, malignancies, major adverse cardiovascular events, tuberculosis, or serious herpes zoster infections; one case of deep-vein thrombosis was reported in a patient with risk factors.

“Our results demonstrated significant clinical improvements in SLE patients taking baricitinib versus placebo with an acceptable side-effect profile,” said Prof Daniel Wallace, Professor of Medicine, University of California and Associate Director, Rheumatology Fellowship Programme at Cedars-Sinai Medical Centre in California, US. “We look forward to progressing baricitinib in further clinical studies as a promising new treatment for people suffering with SLE.”

Meanwhile, a separate study showed that the live attenuated shingles vaccine was well tolerated and provoked an expected antibody response in stable SLE patients not receiving intensive immunosuppression.

Patients with SLE are 10 times more likely to contract shingles compared to healthy individuals and it can also affect them at an earlier age.

However, specific guidelines on the use of the shingles vaccine in SLE patients have been lacking, largely due to a theoretical concern of vaccine-induced infection, as well as a lack of clinical or experimental data upon which to base recommendations.

The study presented at EULAR 2018 included 90 patients with stable SLE who were not receiving intensive immunosuppression. All participants had a history of herpes zoster/chickenpox and were randomised to receive shingles vaccine or placebo. After six weeks, antibody levels in the vaccine group increased by 59.8 per cent versus a reduction of 2.1 per cent in the control group (p=0.01) demonstrating the effect of the vaccine. No serious adverse events were reported and none of the patients had clinical shingles infection post-vaccination.

“This is the first randomised, controlled trial to study the shingles vaccine in individuals with SLE. We hope our results will inform guidelines and ultimately lead to the safe administration of the vaccine in appropriate SLE patients to reduce the burden of shingles in these individuals,” said study author Dr CC Mok, Department of Medicine, Tuen Mun Hospital, Hong Kong.