Rheumatoid Medicine Trends Move to a Different Beat


Biologics, JAK inhibitors, and opioid alternatives all served major payoffs in the field in the 2010s.


While other fields like cardiovascular medicine or orthopedic care seemed to move in staggered step—discovery, application, advancement, repeat—rheumatology’s beat was more prolonged. The field’s great work done in the decade prior; this decade was about reaping it.

Still, if rheumatology in the 2010s was defined by those middle 2 steps—application, advancement—then it will be remembered as a major success for specialists.

The Embrace of Biologics

From a boom in biologics, to the introduction of an orphan drug class, to even redefining pain management for chronic patients, rheumatology has moved in due time from a field in need of answers—to one that sets the model.While the entire field may not have been aware, treatment algorithms for rheumatologic conditions were forever altered in 1998 with the US Food and Drug Administration (FDA) approval of etanercept (Enbrel) for rheumatoid arthritis.

Since then, 8 other biologic disease-modifying anti rheumatic drugs (BDMARDs) have received FDA approval for the treatment of rheumatoid arthritis. All but 2 of these approvals came before 2010.

Since etanercept was approved 21 years ago, the trends have shown developers will seek approval for rheumatoid arthritis before evaluating a treatment’s efficacy and safety for other rheumatic conditions—specifically, psoriatic arthritis and ankylosing spondylitis. With 10 FDA-approved biologic treatments for psoriatic arthritis available and other conditions such as osteoarthritis still without any approved treatments, the question of whether development of biologics for these conditions will continue or come to an end.

Well-regarded rheumatology expert Philip Mease, MD, director of Rheumatology Research at Swedish Rheumatology Research Group and clinical professor at the University of Washington School of Medicine, told MD Magazine® the development of biologics will continue. Overall, it’s going to be positive additions to physicians’ toolkits.

Holding a Better Hand with JAKs

“What tends to happen is that, as a company comes up with a new mode of action that looks like it's going to be successful as an indication—that's great,” Mease said. “But the what they may end up doing that is having slightly higher thresholds of efficacy and better safety that they internally decide they need to meet, in order to compete against a broadening field of available options.”One potentially game-changing group of therapies that have been viewed with skepticism by some rheumatologists, are Janus kinase (JAK) inhibitors. In addition to alleviating patient burden, JAK inhibitors could also be used to partially fill a large gap in treatment in the form of patients who are resistant or refractory to treatment with other BDMARDs. Unlike TNF-inhibitors, which make up the majority of BDMARDs approved for rheumatoid arthritis, JAK inhibitors address inflammation from the inside of cells, and are taken orally, rather than intravenously.

While some in the field appear to be skeptical of JAK inhibitor efficacy—as the first approval came just 7 years ago in 2012, and only 3 are now approved for rheumatoid—Mease feels this sense will soon fade. Rheumatologists will soon realize the potential, and ultimately, the need for these treatments.

“I’m thinking that, as more of this high quality data starts to appear, and as clinicians gain more experience using their medications—and indeed, have pretty good safety results with the drugs—that they're going tend to be more comfortable and interested in using them,” Mease said. “I can tell you that patients are very interested in the idea of once-a-day oral.”

Walking the Line of Opioids

There’s been no greater news story in public health than the opioid crisis in recent memory. Often lost in the headlines and newscasts—in the endless stories of addiction, lawsuit, and political response—is how patients and physicians are almost always left alone to manage the epidemic at the heart at the issue, to bear the burden of public distrust and expert scrutiny behind any resolution.

Media has painted an image of the average American opioid user as a post-surgery or injury patient; seldom does the public think of patient with a chronic disease whose greatest symptom—day in, day out—is pain. As a result, these patients with rheumatic disease and their caregivers are among the most adversely impacted by every new response and policy to the public health crisis.

Historically, opioids were never considered a first-line treatment for chronic pain sufferers. But it was not unheard of for a patient to be prescribed opioids long-term after failing to achieve desired response from other treatments.

Now, with opioids now serving as medicine’s newest boogeyman, rheumatologists are actively avoiding the prescription—for better or worse.

“It's now frowned upon to use opioids in a chronic way and, not only frowned upon: there's this sense that there's somebody watching over your shoulder, ready there to slap your hand if you get into chronic opioid prescription,” Mease said.

Daniel Clauw, MD, professor of medicine and director of the Chronic Pain and Fatigue Research Center at the University of Michigan, has been on the frontlines of developing treatments and managing chronic pain for decades. He pointed out to MD Mag that while the opioid crisis sprung the field into the middle of a controversy with few found resolves, it’s also the impetus behind many non-opioid pain relievers that have been seen increases in use, including SNRI therapies, NSAIDs, and other non-opioid analgesics.

One non-opioid option Clauw believes could have a measurable impact going forward are those derived from cannabidiol (CBD). Yet, while he sees incredible potential with the use of CBD for treatment of many conditions, including chronic pain, it is an area where Clauw urges caution going forward.

Clauw played an integral role in the Arthritis Foundation’s acceptance of CBD as a potential therapy, but he maintains it’s overuse could coincide with the spread of misinformation—diiving CBD use to a rate similar with that of opioids in America.

The Next Decade

“We and others are doing a lot of studies with CBD, but I think CBD is a component of cannabis that is that we know is quite safe, and appears to be somewhat effective in different pain conditions,” Clauw said. “It's going to take a while to educate all patients and providers.”For all the application and advancement this decade has provided, there are still a number of areas with unmet needs in rheumatology. Notably, education is lacking among non-specialists— as is the need for more reliable biomarkers to aid in early disease identification.

The recent onus of interdisciplinary work in medicine has caught on quickly in rheumatology and rheumatologists and patients have seen this pay dividends. Mease has observed his patients are typically younger than they had been in decades past. Much of this has been caused by improved knowledge among primary care providers, non-physician practitioners, and patients.

Still, to improve early diagnosis and subsequent treatment, the longtime expert emphasized the need to place more emphasis on education. This, combined with development of novel biomarkers—whether they are blood- or imaging-based—will provide experts with newfound knowledge of rheumatic disease progression, and a deeper team of caregivers, akin to other fields.

Addressing these spaces of need can push the treatment of rheumatic conditions toward a new cycle of discovery, application, advancement, and repeat, in the 2020s.

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Elizabeth Cerceo, MD | Credit: ACP
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