Authors Argue for More Personalized Rheumatoid Arthritis Care

Rheumatoid arthritis (RA) can look very different from one patient to another, so treatment of the disease must also evolve from a one-size-fits-all approach into a new, personalized medicine paradigm.

Such is the argument of a new opinion piece published in RMD Open by Judith Heutz, MD, and Pascal Hendrik Pieter de Jong, MD, PhD, both of Erasmus University Medical Center in the Netherlands. In the article, the co-authors argued that investigators should leverage information about the different subtypes of the disease to create more targeted treatment strategies.

“[Personalized medicine] allows us to develop treatments that are particularly effective for a subgroup of patients,” they wrote. “Problems [such] as undertreatment as well as overtreatment and accompanying (serious) adverse events might be circumvented by this approach.”

The authors said the current approach relies on early diagnosis and early intensive therapy, typically with methotrexate and glucocorticoids as first-line treatment. If the treatment does not work, prognostic factors are used to determine which treatment option to administer next, usually a disease-modifying anti-rheumatic drug (DMARD). The investigators said this second-line decision strategy marks the beginning of a personalized approach, although they said it leaves much to be desired.

“Still, current treatment initiation and intensifications are largely based on a trial and error approach,” the authors said. “As a result, 50%–60% of patients will not reach remission after DMARD initiation and >60% will need ≥3 treatment intensifications to reach the treatment goal.”

On the other hand, patients who respond well to treatment face an opposite problem: potentially being over-treated when they could theoretically improve with less-intensive therapy, they wrote.

“To overcome this risk of overtreatment and undertreatment, and possibly accompanying (serious) adverse events, we need to predict how patients with RA will respond to their therapy,” the investigators said.

In early phases, Heutz and de Jong suggested dividing RA into 3 clinical phenotypes. The first, undifferentiated arthritis, would include patients whose cases do not meet the 1987 or 2010 classification criteria for RA. The remaining patients could be grouped based on the presence or absence of autoantibodies. The investigators said differences in prognosis and pathophysiology among patients in these groups suggest they might respond differently to treatments, although they said more work would need to be done to understand which strategies work best for which group. For now, they said, the early evidence suggests patients with undifferentiated or autoantibody-negative RA could be good candidates for less-intensive treatment.

Soon, though, the authors said physicians may be able to look at biomarkers to help select the optimal treatment for patients, such as whether to prescribe a biologic or targeted synthetic DMARD. They said existing research, though limited, offers hope that such an approach would lead to meaningful results.

“Prediction of treatment response at initiation or as soon as possible thereafter is vital for improving remission rates and/or drug survival,” they wrote. “Fortunately, more and more evidence is emerging which might help the treating rheumatologist to choose the most effective treatment in the near future.”

Still, Heutz and de Jong said the implementation of personalized RA therapy will remain “hampered” until more evidence, including randomized controlled trials, is collected on the efficacy of various approaches for various patient subgroups. The authors said such evidence needs to be developed sooner, rather than later.

“With the wide range of available treatment options and the need for early effective treatment, personalized medicine should be our priority,” they concluded.

Reference:

Heutz J, de Jong PHP. Possibilities for personalised medicine in rheumatoid arthritis: hype or hope. RMD Open. Published online October 14, 2021. doi:10.1136/rmdopen-2021-001653