Persistence rates highlight unmet need for effective lupus therapies

Prof Eric Morand

Patterns of medication use for lupus in a large cohort of patients confirm the unmet clinical need for new therapies.

Data from the Asia-Pacific Lupus Collaboration was used to assess treatment persistence in 2,860 patients across 19,804 visits between 2013 and 2018.

The study, published in Arthritis Care and Research, found triple therapy – prednisolone, an antimalarial and immunosuppressive agent – was the most commonly observed treatment (31.4% of visits).

Dual therapy was the next most common treatment approach with the combination of prednisolone and an immunosuppressant observed in 20.5% of visits and prednisolone and an antimalarial in 18%.

Monotherapy especially with an immunosuppressant (1.6% of visits) was the least common treatment.

Comparing time to discontinuation of treatment, the study found antimalarial persistence was the highest of all drug categories – with 75% persistence at 1,267 days.

Prednisolone treatment persistence was also prolonged – 75% at day 1,048 and >50% persistence at 1,500 days of follow-up.

Treatment survival was lowest for immunosuppressive drugs – 75% for the most commonly used mycophenolate mofetil (MMF) at day 175.

“The observation of high persistence of antimalarial use was expected and in line with treatment guidelines, but we interpret the high persistence of prednisolone use and low persistence of immunosuppressant use to imply limited long-term utility of immunosuppressants and resulting reliance on long term glucocorticoids,” the study authors said.

They found patients with high disease activity (AMS ≥ 10) had statistically significantly higher hazard ratios of discontinuation of medications, including antimalarials, azathioprine, ciclosporin, tacrolimus, and leflunomide.

“This suggests that treating physicians were more likely to use combination medications in patients with more active disease, but also indicates that these combinations were not able to control disease in those cases,” the investigators concluded.

Switching due to inefficacy

Senior investigator Professor Eric Morand, from Monash University, told the limbic that medication persistence was a useful combined surrogate for both efficacy and tolerability.

“Although we don’t record it in our database, my belief is that inefficacy is the main reason for switching between drugs,” he said.

The low rate of monotherapy use was an indication that none of the medications were good enough to use alone.

“With prednisolone, we’d rather not use it but we use it because the other drugs are not good enough. The persistence of that drug just shows that we lack alternatives.”

“The persistence of antimalarials is a good thing – we think that is a safe, well tolerated and effective mild drug. On its own though it’s rarely enough.”

Professor Morand said many patients with rheumatoid arthritis received benefit from methotrexate.

New treatment guidelines for rheumatoid arthritis reinforce the primacy of methotrexate for the treatment of that disease.”

However in comparison, lupus patients were underserved.

“Our current package of medications is not okay. The fact patients still have active disease despite triple therapy and the fact that immunosuppressants keep being stopped or changed probably due low efficacy tells us that we need better.”

“The high turnover of immunosuppressants combined with the high persistence of steroids, signifies to me the great need for better treatments such as biologics which we hope will emerge.”

The study showed a low use of biologics including rituximab (2%) and belimumab (1.3%).

“That does not mean we don’t want them; it means we don’t have them,” Professor Morand said.

“There is only one approved biologic for lupus and that is belimumab. It’s TGA approved in Australia but not PBS listed therefore it had a very low uptake.”

“Currently regulators are reviewing the potential approval of anifrolumab. It’s not yet approved anywhere but hopefully this year.”

Professor Morand said the prospect of new biologics for lupus in the coming years raised the issue of which patients will qualify.

“We know in rheumatoid arthritis, you have to have failed two drugs before you are allowed to use a biologic. We’re not sure that is sensible in a disease where all the immunosuppressants basically fail so often and force patients to try drugs that we know are not very good. That might not be the best outcome for patients.”

“This paper is an attempt to put evidence out into the space… that payers and regulators can consider as they reach these decisions.”

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