Better lupus treatments? Two drugs show promise in clinical trials

Date:

  • Lupus is an autoimmune disorder that causes a range of symptoms, some of which can be severe.
  • It is more common in females, who account for 90% of cases.
  • Once doctors confirm the diagnosis, they use treatments such as steroids to reduce inflammation, preventing organ damage and reducing flare-ups of symptoms. However, these treatments can have side effects, particularly with long-term use.
  • Now, two drug trials have shown promising results for the treatment of lupus.
  • In a long-term phase 3 trial, anifrolumab, an intravenous monoclonal antibody, and in a phase 2 trial, deucravacitinib, an oral treatment, emerged as both safe and effective.

Autoimmune diseases occur when the body’s immune system, which defends against disease, starts to attack healthy tissues.

There are more than 80 known autoimmune diseases, which can affect almost any part of the body. Their causes are unclear, but may include genetics, infections, and environmental factors.

One of the most common autoimmune disorders is lupus, the most frequent form of which is systemic lupus erythematosus. This condition causes inflammation of the skin, joints, and, in severe cases, internal organs, and the symptoms range from mild to life-threatening.

Lupus affects around 5 million people worldwide, and it occurs much more often in females than males.

Common symptoms of lupus include:

  • muscle and joint pain
  • a butterfly-shaped rash on the face
  • sun sensitivity
  • tiredness
  • fever.

To treat lupus doctors may prescribe hydroxychloroquine, which is also a malaria drug, corticosteroids, and immunosuppressants. People with systemic lupus erythematosus also benefit from following a healthy diet and avoiding smoking and excessive alcohol consumption.

Now, in a long-term phase 3 drug trial whose results appear in the journal Arthritis and Rheumatology, researchers have found that a monoclonal antibody, anifrolumab, appears both safe and effective in treating systemic lupus erythematosus.

“This study found no long-term safety issues using anifrolumab to treat active [systemic lupus erythematosus] — a chronic condition — implying the clinician can prescribe this treatment over a long period of time with almost no concern that patients will develop long-term adverse events, also known as side effects.”

– Dr. Kazem Kazempour, CEO and president, Amarex Clinical Research

And in a phase 2 drug trial, whose results also appear in Arthritis & Rheumatology, deucravacitinib, an oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2), has shown similarly positive results.

The long-term extension study followed earlier work investigating anifrolumab as a treatment for systemic lupus erythematosus. The two previous trials, Treatment of Uncontrolled Lupus via the Interferon Pathway 1 (TULIP-1) and TULIP-2, had shown a positive benefit-risk profile for the drug.

Anifrolumab is a fully human monoclonal antibody that inhibits signaling of all type I interferons. Sustained production of type 1 interferons can cause the immune system to attack healthy tissues causing damage and disease.

This 3-year trial explored the safety and tolerability of anifrolumab in people with systemic lupus erythematosus who had completed the earlier TULIP trials. It is the first double-blind, placebo-controlled long-term trial of this drug with systemic lupus erythematosus patients.

The 547 participants in the long-term extension study had received different medication regimes in the previous TULIP trials — placebo, 150 milligrams (mg) anifrolumab, or 300 mg anifrolumab. All participants who had previously received either dosage of anifrolumab (324 people), now received 300 mg anifrolumab intravenously every 4 weeks.

Those who had previously received placebo were randomly allocated to 300 mg anifrolumab or placebo. Of this group, 111 received anifrolumab in the long-term extension study, with the remaining 112 continuing to receive placebo.

The extension study was designed to reflect real-world clinical practice, allowing investigators to add or change background standard care treatment during the trial, therefore some participants remained on glucocorticoids or immunosuppressants, but the numbers were similar in each group.

To assess the safety of anifrolumab, researchers recorded the number of serious adverse events that occured throughout the study. They then recorded the total no of adverse events per 100 patient-years, or exposure-adjusted incidence rates.

During the long-term extension study, in the anifrolumab groups, exposure-adjusted incidence rates for any adverse event were 33.1, compared with 37.6 for the placebo group. For serious adverse events, the figures were 8.5 for anifrolumab, and 11.2 for placebo.

When assessing efficacy, the researchers found greater mean improvement in symptoms in the anifrolumab 300 mg group than in the placebo group. This improvement was sustained, with disease activity remaining low in the anifrolumab group throughout the study.

Participants who received anifrolumab were also able to reduce the treatment with glucocorticoids. Long-term glucocorticoid use has been associated with side effects such as cardiovascular events, and osteoporosis with fractures.

“These data show an acceptable long-term safety profile of anifrolumab in [systemic lupus erythematosus] in addition to sustained improvements in disease activity and reduction in glucocorticoid use. Taken together, the findings support the favorable benefit–risk profile of long-term anifrolumab as a treatment option for patients with moderate-to-severe [systemic lupus erythematosus].”

– Dr. Kazem Kazempour

Corresponding author on the phase 3 trial, Dr. Hussein Al-Mossawi, of AstraZeneca, noted that “managing systemic lupus erythematosus is challenging, due to the complexity of the disease itself, as well as from treatments like oral corticosteroids that can reduce disease activity, but also place a significant burden on patients when used in high doses long-term.”

“These new data from the TULIP extension trial — the longest placebo-controlled clinical trial performed in lupus to date — support the benefit-risk profile of anifrolumab seen in previous trials, now over 4 years,” he commented.

Dr. Kazempour agreed:

“Based on the above safety, tolerability, and long-term efficacy data, yes, anifrolumab appears to be an effective treatment for patients with lupus. The findings from this study are significant because they are based on a large-size ‘randomized, placebo-controled’ clinical trial conducted across 176 study sites in 24 countries.”

“This study provides the necessary evidence for anifrolumab to be adopted as a long-term adjunct treatment for active [systemic lupus erythematosus] […] Further evidence will be needed post-marketing to confirm an even longer long-term safety and efficacy profile,” he added.

The second study also achieved encouraging results in the treatment of SLE.

In this 32-week, phase 2 drug trial of the oral treatment, deucravacitinib, those on the active drug showed greater improvement in symptoms and similar rates of adverse events to those on placebo.

Participants on all dosages of deucravacitinib responded better than those on placebo, but the effect was greatest in those on the lowest trial dose of 3 mg twice daily. These participants showed a 58% SRI-4 response — a measure of improvement in symptoms — compared with 34% for those on placebo.

So for those living with lupus, the future could soon be looking brighter.

Read the full article here

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