OMAHA, NE—The most common form of inflammatory arthritis—gout—affects about eight million Americans. The disease causes intensely painful flares, but despite the availability of several drugs to manage this chronic, incurable condition, ongoing adherence to therapy remains very low, with estimates ranging from 10% to 46%.

The standard therapies for gout work quite well, making the lack of adherence a little puzzling to researchers.

“Uric acid-lowering treatments, such as allopurinol or febuxostat, are highly effective for patients suffering from gout,” said Ted R. Mikuls, MD, of the Division of Rheumatology at the VA Nebraska-Western Iowa Health Care System. “By lowering, then maintaining uric acid levels, the risks of flares are greatly reduced and in many cases are eliminated.”

High uric acid levels can lead to the development of monosodium urate monohydrate crystals. Deposition of these crystals in joints, most often the big toe, cause the distinctive inflammation and pain of the disease. Crystals can form in soft tissue as well and, when they develop in kidneys, can cause renal damage.

Preventive treatment aims to keep serum urate below 6.0 mg/dL.

Rheumatologists typically prescribe nonsteroidal anti-inflammatories, steroids, colchicine and adrenocorticotropic hormone to treat acute gout or flares, but these medications do not lower uric acid levels or prevent future flares.

“The reasons [for low adherence to preventive regimens] are not entirely clear. Patients and providers may not always understand the role of these medicines, which are typically used for prevention but not for the treatment of the flares that characterize this arthritis,” Mikuls told U.S. Medicine. “Therefore, the potential benefit of this treatment is not always clearly articulated.”

Nonadherence to recommended long-term therapy comes with significant costs for patients and the health system. “Gout flares can be extremely debilitating, can reduce the quality of life and lessen productivity among sufferers,” Mikul noted. “These therapies also prevent joint damage that results from flares and prevents the formation of uric acid deposits (called tophi) that develop near or in the joints.”

To increase adherence and improve outcomes for patients with gout, Mikuls and his colleagues implemented a pharmacist-led intervention. In a study published in the American Journal of Medicine, they discussed the program’s successes while recognizing the need for additional patient outreach and engagement.

Finding a way to increase adherence to gout therapy is particularly important for the VA and the veterans it serves. While the precise number of veterans with gout is not known, “we do know gout is far more common in men than women. It increases with age and with select chronic health conditions, such as chronic kidney disease which is common among U.S. veterans. Therefore, we believe gout is very common among veterans in VA care, a burden we hope to more clearly define with ongoing research,” Mikul noted.

The trial included 1,463 gout patients starting on allopurinol randomized by site to usual care (50 sites) or a highly-automated, one-year intervention (51 sites). Physicians set allopurinol doses at their discretion. Following receipt of first prescription, participants at the intervention sites were managed by a pharmacist following an algorithm developed through expert consensus, which used a treat-to-target approach with urate monitoring and allopurinol dose escalation, as indicated. 

Staying on Therapy

The intervention arm also utilized an interactive voice response system to determine whether patients adhered to the prescribed regimen, remind them of prescription refills, and offer encouragement to stay on therapy. Participants who did not pick up refills, failed to respond to automated calls, or did not have lab monitoring on the established schedule, received telephone calls from the study pharmacist to probe for issues, provide assistance and answer any questions.

Participants receiving usual care were prompted to have a serum urate assessment at baseline, if they had not had one in the previous three months and again at one and two years after study initiation.

Patients in the intervention arm had 68% increased odds of adhering to therapy, 50% vs 37% for those who received usual care. They were also twice as likely to reach serum urate goal of less than 6.0 mg/dL at one year, 30% vs 15%.

One year after the intervention ended, patients in the intervention arm continued to have lower urate levels but no greater adherence than those who received usual care. Those in the intervention arm had a 6% to 16% lower rate of gout flares in year two, though the difference did not rise to statistical significance. 

While this “light-touch, low-tech intervention was efficacious, additional efforts are needed to enhance patient engagement in gout management and ultimately to improve outcomes,” the authors concluded.

“We believe interventions, such as in-person education and counseling will be more effective than automated telephone calls as was used in the study,” Mikul said. “We currently have a larger study underway exploring that.”

Looking at the data in Year Two provided critical take-aways for the researchers. On the one hand, the drop in adherence “shows that maintenance is needed in order to sustain the early benefit we saw. Methods such as a yearly visit with an ambulatory pharmacist, a nurse, a primary provider and remote delivery using telehealth technology are examples of possible maintenance,” to consider in future studies, Mikul noted.

On the other hand, the persistence of a benefit in terms of urate levels following the intervention demonstrates that “the benefit of uric acid lowering therapy often takes time to observe,” he added. 

That may be information patients need to know up front. “For example, most studies suggest that periods of two years or longer are often needed to yield clinical benefit from these treatments in terms of flare reduction,” Mikul explained. “For some, this period may be much shorter, and they may see a benefit earlier. Our results reflect that those perceiving the most benefit were more likely to persist with treatment, while others not perceiving benefit in the first year, were more likely to be nonadherent.”

Mikuls TR, Cheetham TC, Levy GD, Rashid N, Kerimian A, Low KJ, Coburn BW, Redden DT, Saag KG, Foster PJ, Chen L, R Curtis J. Adherence and Outcomes with Urate-Lowering Therapy: A Site-Randomized Trial. Am J Med. 2019 Mar;132(3):354- 361. doi: 10.1016/j.amjmed.2018.11.011. Epub 2018 Nov 29.