It's all stuck together, and it's just a mess in there
For the millions living with inflammatory bowel disease — and especially for the fraction whose bodies have resisted every available treatment — medicine has long offered diminishing returns and, eventually, the surgeon's knife. Two clinical trials now suggest that pairing two already-approved drugs may open a door that had seemed permanently closed, nearly doubling remission rates for the most treatment-exhausted patients. The findings do not yet constitute a cure, nor are they the final word, but they represent something rarer in chronic illness: a credible reason for hope grounded in rigorous evidence.
- For patients like a 34-year-old food writer who has endured 20 abdominal surgeries since childhood, the pipeline of viable drug options has not just narrowed — it has nearly vanished.
- The combination of golimumab and guselkumab pushed remission rates to nearly 50% in the most resistant Crohn's patients, compared to roughly 23–27% on either drug alone — a gap too large to dismiss.
- These are still phase 2b results, meaning larger confirmatory trials must launch and succeed before any formal approval pathway opens, likely keeping the combination out of standard care for years.
- Even if phase 3 trials succeed, physicians face a structural obstacle: insurers are reluctant to cover two separate advanced medications simultaneously, forcing doctors into exhausting appeals on behalf of their sickest patients.
- The field is now watching whether clinical evidence will be enough to move both regulators and payers, or whether the most desperate patients will remain caught between promising science and an unresponsive system.
Two clinical trials presented this week offer the first rigorous evidence that combining two existing drugs — golimumab and guselkumab — can meaningfully help IBD patients who have run out of other options. The findings matter most for the estimated 10 to 20 percent of patients whose disease has stopped responding to one advanced therapy after another.
Up to 3.1 million Americans live with inflammatory bowel disease, a condition in which the immune system attacks healthy digestive tissue, producing chronic pain, diarrhea, fatigue, and weight loss. It takes two main forms — Crohn's disease and ulcerative colitis — each targeting different parts of the intestinal system. The trials enrolled patients with moderate-to-severe disease who had already failed at least one class of advanced treatment. Among Crohn's patients who had exhausted two or more drug classes, nearly half achieved remission on the high-dose combination after 48 weeks — compared to roughly a quarter on either drug alone. The ulcerative colitis trial showed a similar pattern, with no meaningful increase in safety concerns.
For those who exhaust drug options, surgery becomes the alternative. Tess Koman, a 34-year-old food writer diagnosed with Crohn's at age 7, has undergone 20 abdominal surgeries and has roughly half her bowel remaining. She has tried multiple drug classes with mixed results, including allergic reactions to biologics. A working combination therapy could, for patients like her, mean avoiding the next operation.
The path forward is not without obstacles. These are phase 2b trials; larger phase 3 studies are expected to begin recruiting later this year before any approval can be pursued. More immediately, the combination does not exist as a single approved drug — meaning physicians would need to prescribe both medications separately and persuade insurers to cover them simultaneously. Specialists at institutions like the Mayo Clinic already attempt dual therapy in severe cases but describe a grueling appeals process. Whether the insurance system will move in step with the science remains the open and urgent question.
Two clinical trials presented this week offer the first rigorous evidence that combining two existing drugs can help patients with inflammatory bowel disease who have run out of other options. The findings arrive as a potential lifeline for a small but desperate population: the estimated 10 to 20 percent of IBD patients whose bodies have stopped responding to one advanced therapy after another.
Up to 3.1 million Americans live with inflammatory bowel disease, a condition in which the immune system mistakenly attacks healthy tissue in the digestive tract. The disease manifests as chronic diarrhea, abdominal pain, fatigue, nausea, and unexplained weight loss. It comes in two main forms—Crohn's disease and ulcerative colitis—each attacking different parts of the intestinal system in different ways, though the symptoms often feel identical to those suffering through them.
The two trials tested whether combining golimumab and guselkumab—both already approved drugs that work through different biological mechanisms—could outperform either drug alone. One trial followed 693 patients with Crohn's disease; the other tracked 572 with ulcerative colitis. All participants had moderate-to-severe disease and had already failed at least one class of advanced therapy. The results were striking, particularly for the most stubborn cases. Among Crohn's patients who had exhausted two or more advanced drug classes and received the high-dose combination, nearly half achieved clinical remission after 48 weeks. That compared to 27 percent on guselkumab alone and 23 percent on golimumab alone. The combination group also showed fewer intestinal ulcers and less inflammation overall, with no meaningful increase in safety concerns.
Dr. Uma Mahadevan, a gastroenterologist at the University of California, San Francisco, called the findings "quite significant." They represent the first hard data from randomized controlled trials backing the use of combination therapy for IBD—a concept that makes intuitive sense but had lacked rigorous proof until now. The ulcerative colitis trial showed a similar pattern of benefit. Yet these are phase 2b trials, designed to confirm efficacy and find the right dose. Larger phase 3 trials, expected to begin recruiting patients later this year, will be needed before the combination can move toward approval.
For patients who have exhausted drug options, the alternative is surgery. Ulcerative colitis patients can often achieve remission by having their colon removed entirely. Crohn's disease is trickier—it can strike anywhere in the digestive tract, so surgeons typically remove only the affected section. But the disease often returns. Tess Koman, a 34-year-old food writer and editor, has undergone 20 abdominal surgeries since her Crohn's diagnosis at age 7. She has roughly half her bowel remaining. "It's all stuck together, and it's just a mess in there," she said, describing the cumulative damage from both the disease and years of surgical intervention. She has tried multiple drug classes with mixed results, including allergic reactions to biologics. For patients like her, a working combination therapy could mean avoiding another operation.
Yet a practical barrier looms. The experimental combination does not yet exist as a single approved drug. Doctors would have to prescribe golimumab and guselkumab separately—and convincing insurance companies to cover two different medications for one patient remains difficult. Dr. Victor Chedid, an IBD specialist at the Mayo Clinic, noted that some physicians already attempt dual therapy in select severe cases but must wage repeated appeals with insurers to make the case. "Sometimes you have to do multiple appeals with insurance companies to make the case that your suffering patient who has more severe disease needs dual therapy," he said. Dr. Maria Abreu, lead author of the ulcerative colitis study, expects that once doctors absorb these findings, they will begin proposing combination approaches for patients not responding to single agents. The question is whether the insurance system will let them.
Citas Notables
These studies are really quite significant— Dr. Uma Mahadevan, gastroenterologist at UCSF
Sometimes you have to do multiple appeals with insurance companies to make the case that your suffering patient needs dual therapy— Dr. Victor Chedid, Mayo Clinic IBD specialist
La Conversación del Hearth Otra perspectiva de la historia
Why does combining two drugs that already exist matter more than just developing one new drug?
Because these drugs work through different mechanisms—one targets one protein driving inflammation, the other targets a different one. Together they hit the disease from two angles at once. It's not about inventing something new; it's about using what we have more intelligently.
But if doctors already knew this might work, why did they need these trials?
Intuition isn't evidence. You can theorize all day that two drugs might be better than one, but insurance companies, regulators, and doctors need to see the numbers. These trials gave them those numbers for the first time.
The patient profiled—Tess Koman—has had 20 surgeries. How does that even happen?
Crohn's disease is relentless. It can come back after surgery. And each surgery creates scar tissue, adhesions, complications that often require more surgery. She's been fighting this since childhood. A working drug combination could have spared her some of that.
What's the insurance problem, exactly?
Right now, if a doctor wants to prescribe two different biologics, the insurance company has to approve both. They often push back, asking why one drug isn't enough. Doctors have to appeal, sometimes multiple times, to convince them the patient is sick enough to justify the cost of two medications.
So even if these phase 3 trials succeed, patients might still struggle to get the treatment?
Exactly. The clinical promise is one thing. The practical reality of actually getting patients access is another.