Lupus is a potentially fatal autoimmune disorder that impacts roughly 5 million people worldwide, and yet it still has no known cause or cure.
Today, most treatments come with a whole bunch of adverse side effects, and given how little we know, finding new avenues for medicine has proved extremely difficult.
In the past six decades, only one drug for lupus has been approved by the United States Food and Drug Association and it's still unavailable to many. Now, an international three-year clinical trial offers the first real hope for patients in half a century.
The Phase 3 trial, called TULIP-2, tested a drug called anifrolumab on a randomised selection of 180 people with lupus, giving them 300 mg every four weeks for 48 weeks.
Compared to the placebo, which was given to a further 182 participants who also had lupus, the authors say anifrolumab produced a statistically significant and clinically-meaningful reduction in the disease.
After 52 weeks, not only only did this drug reduce autoimmune activity in the relevant organs of many of the treated patients, it also reduced the rate of flare-ups - which include fever, painful joints, fatigue and rashes - and lessened the need for steroids.
"There is now a strong body of evidence demonstrating the benefit of anifrolumab, and we look forward to bringing this potential new medicine to patients with systemic lupus erythematosus as soon as possible," says Mene Pangalos, the executive vice president of BioPharmaceutical R&D.
Even when no virus infection can be found, recent studies show the vast majority of lupus patients produce excess Type 1 interferon, which is an immune protein linked to the development of white blood cells.
Previous attempts to block this protein have failed, but anifrolumab blocks the receptors for this protein instead and not the molecule itself.
Another clinical trial that tested this drug, called TULIP-1, couldn't support any particular benefits based on its specific method, although there were signs that it might help improve the health of certain organs.
The smaller second trial has now explored this second outcome further - known as the British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) - and the results look much more promising.
Unlike TULIP-1, TULIP-2 showed benefits on both the BICLA and SRI index.
"Measurement of treatment response in [systemic lupus erythematosus] has been very problematic and this represents a kind of second breakthrough of this trial," says rheumatologist and lead researcher Eric Morand from Monash University.
It's still unclear why TULIP-1 and TULIP-2 produced different results, especially since they were nearly identical. But an accompanying editorial explains they might have differed because various elements of lupus were weighted differently. One of the assessments, for example, only captures partial responses while another only captures complete responses.
"Therefore, the effect of a drug on particular disease features may produce superior results with one end point and not another," the editorial reads.
So far, three clinical trials in total have tested anifrolumab, and the results for five of the six outcomes favoured the drug over the placebo. Given the desperate need for treatment, many in the lupus community are urging regulators to consider trials that allow greater flexibility in defining success.
"For example," the authors of the editorial write, "perhaps a benefit with respect to just one of two end points — the SRI or the BCLA — needs to be observed to declare a drug effective in this complex disease."
This could accelerate drug development until we know better what response measures and biomarkers are most useful when trialling lupus medication.
More research is needed for anifrolumab before we can say for sure whether its benefits outweigh its side-effects in the long run. Some patients taking the drug were more at risk of bronchitis and upper respiratory infection and the risks beyond 52 weeks are still unclear.
"As clinicians we need new medicines for this complex and difficult-to-treat disease," says Morand.
"These exciting results from the TULIP 2 trial demonstrate that, by targeting the type I interferon receptor, anifrolumab reduced disease activity in patients with systemic lupus erythematosus."
The study was published in NEJM.