For many people with inflammatory arthritis, the introduction of biologic drugs two decades ago was life-changing.
One morning in 2001, Suzanne Schrandt woke up feeling as though something were missing, but she couldn’t put her finger on it. “Was there an appointment I was meant to attend?” she wondered. “Had I misplaced my wallet? My car keys?” Schrandt, who was 24 at the time, walked to her car to leave for work. She gripped the door handle with both hands and – as usual – braced herself for the pain that opening the car door caused. Then, “Whoosh! I whipped the door open almost violently, throwing myself a bit off-balance, and finally [realized] that the missing thing was pain,” she recalls.
Diagnosed 10 years earlier with polyarticular juvenile rheumatoid arthritis, Schrandt had scarcely known a day without pain for more than a decade, despite the treatments that began shortly after her 14th birthday. So when her doctor prescribed infliximab (Remicade), a new type of drug given by infusion, she had been skeptical. But that morning after her first infusion, she became a believer, and she was repeatedly amazed in the following weeks as she went about her daily activities without pain.
“My rheumatologists have told me time and again there is no way I could have had such a dramatic response within a 24-hour period,” Schrandt says. “But all I know is what I felt that day, and it was nothing short of miraculous.”
For countless people like her, infliximab and the other so-called biologic response modifiers – or biologics, for short – have been miracle drugs, controlling pain, improving quality of life and slowing or stopping the progress of a disabling disease when nothing else could.
A Different Kind of Drug
Biologics are not like synthetic, conventional disease-modifying antirheumatic drugs (DMARDs), which are created by combining specific chemical ingredients in an ordered process. Instead, these drugs consist of large, complex molecules genetically engineered from living organisms, such as viruses, genes or proteins.
Unlike conventional DMARDs, which work in ways that are not well understood, biologics work by interfering with specific cells and pathways of the immune system. Normally, the immune system protects the body against infection and disease. But in people with inflammatory, autoimmune types of arthritis, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile arthritis (JA) and ankylosing spondylitis (AS), the immune system is overactive. Inflammation – part of the immune response – is uncontrolled and doesn’t stop, leading to a cycle of pain and damage to joints. In time, this body-wide inflammation can lead to a host of other problems, including injury to organs and body systems.
For some people, like Schrandt, life with arthritis can be divided into a distinct before and after: the painful life before starting a biologic and the active life after. Rheumatologists, too, speak of “before and after” in terms of the impact biologics have made in treating patients. Before biologics, a diagnosis of rheumatoid arthritis was pretty dismal; for many patients, treatments didn’t work well and caused side effects that at times rivaled those of the disease.
When David Pisetsky, MD, PhD, began practice in the late 1970s, treatments being tried for RA included total lymphoid irradiation, thoracic duct draining and plasmapheresis (a process that involves removing plasma from a patient’s blood).
One of the early treatment staples was aspirin – lots and lots of aspirin, says Dr. Pisetsky, professor of medicine and immunology at Duke University Medical Center and chief of rheumatology at Durham VA Medical Center. It took a minimum of 12 tablets a day to get an anti-inflammatory effect, but 16 was not unusual. “I had one patient I gave 27 aspirin a day because he was a big man,” he recalls.
Getting the dose right to reduce inflammation required blood tests, and often the amount of aspirin needed to ease joint inflammation caused other problems, including ringing in the ears, loss of hearing and gastrointestinal bleeding, a serious, sometimes fatal complication.
Other options – including corticosteroids and gold injections – weren’t necessarily better. Although corticosteroids are potent inflammation fighters, they carry a long list of dangerous side effects, including bone thinning, hypertension, weight gain, diabetes and eye damage – particularly at the high doses initially used – and patients were required to stay on them for long periods of time.
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