Lifesaving it may be, organ transplantation carries a life sentence, so to speak — that is, anyone who receives a donor organ also gets a lifetime prescription for anti-rejection medication.
It’s for good reason: These drugs suppress your immune system’s natural defenses so that your body doesn’t attack (or “reject”) the new organ. But in saving the organ (and your life), they also come with side effects and risks, including potential infections, kidney problems and some kinds of cancer.
Undoubtedly, anti-rejection medications are necessary. But given the risks, is it possible to dial the dose down until they’re not needed at all? Can you be weaned off without your body attacking the transplanted organ later on?
The step-down approach
Such are the questions posed by Optimal, a nationwide research effort now available at Baylor University Medical Center at Dallas. As one of six research centers involved (and the only one in Texas), we’re enrolling liver transplant recipients from the Dallas/Fort Worth area to explore the idea of immunosuppression withdrawal — or stepping down doses until they’re not needed at all.
Beyond studying withdrawal, though, we’re interested in two other key questions: Do some people need anti-rejection medication more than others? And if so, could a blood or liver biopsy someday predict who needs lifelong anti-rejection medication versus who can withdraw their doses over time?
For these questions, we’ll take liver samples (biopsies) from all of our participating patients, studying them closely for potential red flags, or markers, of rejection risk. If we find such markers, it might help us someday determine whether it’s safe to reduce or stop anti-rejection drugs for transplant recipients — on a personalized basis.
So, why the liver?
It’s simple, really. The liver is more robust and can tolerate rejection much better than other organs, should rejection occur. But that doesn’t mean we don’t see applications of this research for other transplanted organs down the line, like the heart or kidneys. We absolutely do.
Making that vision a reality requires capturing the learnings first — and we believe studying the liver offers a promising option to effectively gather the information and data we need.
Three phases of one long-term study
All told, involvement in the study could take up to six years and would include several in-person clinic visits and phone consultations.
For those who qualify, here’s how it will work:
• Screening Phase (1-5 Weeks): During the first few weeks, patients will take part in various exams, tests, a liver biopsy and medical history review to gauge eligibility.
• Immunosuppression Withdrawal Phase (6-12 Months): If patients advance from the screening phase, they’ll then undergo a few more tests, plus a slow reduction in anti-rejection medicines. Previous research has shown that patients have about a 50 percent chance of completing this reduction without rejection, but if it happens, physicians can respond with rejection treatment.
• Follow-Up Phase (3-5 years): As the name suggests, this final phase involves long-term follow-up, including several tests and exams throughout the remainder of the study. And again, if rejection happens, physicians can respond with rejection treatment.
With research like this, it can often take years to draw conclusions — and this one may take up to three years before we see firm early results — but based on what we’ve seen in the past, we’re quite optimistic about the step-down approach to anti-rejection drugs.
The Optimal study is a part of the Immune Tolerance Network (ITN), a group focused on finding new therapies for asthma/allergy, autoimmune diseases, type 1 diabetes and immune tolerance of solid organ transplantation. ITN is funded by the National Institute of Allergy and Infectious Diseases from the National Institutes of Health.