The study team compared the long-term effectiveness of adjuvant treatment with a catechol-O-methyltransferase inhibitor (COMTi), a MAO-Bi or a dopamine agonist in 500 PD patients (mean age, 73) experiencing motor symptoms on levodopa.
Over a median of 4.5 years' follow-up, patients who added a dopamine agonist had a mean mobility score on the 39-item PD Questionnaire (PDQ-39) that was 2.4 points better than that of the combined MAO-Bi and COMTi groups. However, this difference was not significant (P=0.20).
In the comparison between MAO-Bi and COMTi, patients who added a MAO-Bi had a mean PDQ-39 mobility score that was 4.2 points better than that of those who added a COMTi (P=0.03).
"The MAO-B inhibitors produced disease control that was equivalent to that of dopamine agonists, which suggests that MAO-B inhibitors might be underused as adjuvant therapy for the treatment of people with PD," Dr. Richard Gray of University of Oxford and colleagues write in JAMA Neurology.
The researchers caution that adherence to assigned medication was "suboptimal" with only about 50% of participants still receiving their assigned drug class at five years.
"The most frequent reasons for withdrawal from randomized treatment were confusion and psychosis among those receiving dopamine agonists or MAO-B inhibitors and diarrhea among those receiving COMT inhibitors, which are all well-recognized adverse events. Withdrawal from treatment was more common among older patients, suggesting a cautious approach to adjuvant therapy among that population," the study team notes.
The authors of a linked editorial say an important caveat is that there was "no clinically meaningful difference" between the three major classes of adjunctive therapies with regard to five-year PDQ-39 mobility scores and other outcomes.
Dr. Tanya Simuni of Northwestern University Feinberg School of Medicine in Chicago and Dr. Michael Okun of University of Florida Health in Gainesville also caution that "meaningful comparison is restricted by high discontinuation rates across these three classes of agents; these discontinuation rates are largely associated with adverse events, raising the major question of the overall utility of widespread use of adjunctive therapies in this population."
The study also shows that long-term meaningful outcomes including dementia, institutionalization, and mortality, "remain quite unfavorable despite increasing numbers of available adjunctive therapies."
"Possibly the most important, although derived, conclusion of the Gray et al study is that levodopa remains the criterion standard, and there is questionable benefit in the long-term use of any of the currently available adjunctive therapies. However, the limitations of levodopa therapy are also well recognized and, as such, levodopa optimization strategies have been the most actively developed category of experimental therapies in the last decade. Most important, there is an urgent need for therapies that will meaningfully change the disease course," Dr. Simuni and Dr. Okun conclude.
The trial did not have commercial funding.
SOURCE: https://bit.ly/3HfjvO8 JAMA Neurology, online December 28, 2021.
By Reuters Staff
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