Lupus is enigmatic. It can be both mild and severe, visible and hidden, and most importantly, misdiagnosed.
That complexity makes it hard to detect and treat — and even harder to track. Reports suggest over 1 million people in the U.S. live with this autoimmune condition (90% of them women). But with an average of nearly six years to diagnosis and a high rate of misdiagnoses, many remain uncounted, and even experts debate how accurate those numbers are.
That’s part of the problem, noted Karen Costenbader, M.D., director of the lupus program at Brigham & Women’s Hospital. Speaking at the 2025 STAT Summit, Costenbader discussed the spectrum of lupus presentations and how it’s so wide-ranging that clinicians even debate whether lupus is one disease or many.
“Lupus can affect any organ system in the body,” she said, adding that it can manifest in the kidneys, in the skin, the central nervous system, or other areas. Each form can cause different effects, ranging from rashes and hair loss to joint pain and fatigue.
“No two patients have the same disease, so it’s challenging to take care of someone with lupus.”
But lately, researchers have started to crack that code with a more customized approach. With new drug classes and endpoints that prioritize quality of life and patient choice, lupus is entering a renaissance — and many in the field are watching to see what it brings.
Beyond steroids
Despite lupus presenting differently from person to person, historical standards of care regimens have largely not been specifically created for lupus. Treatment typically involves steroids, which, while helpful to control disease, weren’t meant to be used indefinitely: Long-term steroid use can cause irreversible organ damage, bone density issues, infections, and other complications.
And yet, lupus can be a lifelong disease that shifts from remission to flare-up and back again, added Diana Gallagher, M.D., head of clinical development for MS, Immunology and Alzheimer’s at Biogen. That’s why she says creating the current generation of lupus therapies across biologics and small molecules is so critical.
“You see patients with all aspects of this disease, from milder forms to profoundly impacted, even critically ill with lupus,” she said in a STAT Brand Studio interview. “We want to develop medicines that treat them wherever they are in that journey, in the beginning and later stages, mild, moderate, and severe.”
That customized care landscape is already taking shape, with options being developed specifically for lupus and others borrowed from areas like cancer and rheumatoid arthritis. Disease-modifying antirheumatic drugs (DMARDs), Janus kinase (JAK) inhibitors, and B-cell depletion therapies are just a few additions to the expanding toolkit of lupus treatments that span oral drugs, injectables, and infusions.
The end goal with these therapies is to match them with individualized needs — going beyond reliance on steroids toward a new frontier of precision medicine, where lupus treatments are as diverse as the people they aim to help.
“There are a lot of unmet needs still, but it’s exciting that there’s all this interest,” Costenbader said. “More things are expected to be approved in the next couple of years, and then we’ll have choices, and we’ll be at an exciting new place.”
Tailoring trials for disease complexity
Lupus’ underlying complexity has implications for clinical research, and companies like Biogen have had to respond with a refined approach to trial design. At Biogen, that approach draws on decades of experience studying other difficult-to-define diseases such as multiple sclerosis and Alzheimer’s, where careful phenotyping and thoughtful trial design and execution are essential.
One challenge is patient identification. Enrolling the right participants for a hard-to-diagnose disease is never easy. Gallagher noted that Biogen’s trials often use adjudicators who evaluate biopsies to confirm lupus and the specific disease stage.
Another factor is how the trial is conducted. Studying efficacy in a population taking varying doses of steroids, which can attenuate treatment effects, calls for a special protocol design. Carefully monitored steroid tapering is a critical aspect to execution of modern lupus studies, Gallagher added.
“To conduct global Phase 3 trials — of which we’re doing four at Biogen — is quite an endeavor,” she said. “It requires a sophisticated team of folks to do it and really rigorous attention to detail throughout a multi-year, late-stage program. That’s what it takes to get it done.”
Prioritizing what patients want
As trial designs go, there’s also the matter of how people with lupus feel, especially as their condition intersects with professional and personal life.
“They’re worried about day-to-day, the fatigue, the joint pain, can they go to work?” Costenbader said. “They have a lot of practical concerns. This can be a really overwhelming disease … it waxes and wanes over time. There are periods where it gets better, but it’s still there. You have to take medications for life, so patients rightly have a lot of concerns.”
Those lived experiences are pushing researchers toward more patient-centric endpoints in their studies — while harder to measure than a lab value, they’re equally important. Getting off steroids is one common goal, as is reducing pain and fatigue.
“We have public-private partnerships with the FDA and others to figure out how to design these trials and execute these trials in a way that efficiently will bring new medicines to patients, and also do some work to educate ourselves about what’s important to them,” Gallagher said.
“Multiple autoimmune diseases have been here before,” she added, alluding to other conditions like multiple sclerosis and inflammatory bowel disease that have had their own eras of innovation. “Yes, lupus is complicated, but there’s no reason we can’t get there, just like we have in many other diseases.”
