In this study, we found poor adherence to newly-initiated ULDs was common in gout patients, with only 44% of the study population achieving an MPR > 0.80 in the first year of therapy. Predictors of non-adherence included age less than 50 years, fewer comorbid conditions based on the Charlson score, no provider visits specifically for gout care prior to ULD initiation and the use of NSAIDs in the year prior to ULD initiation. These findings suggest that younger and healthier patients with gout may be at particularly high risk for medication non-adherence, potentially due to a lack of experience in managing other chronic conditions or seeking care. In addition, these patients may have a knowledge deficit in how and when to use their medications. We are currently conducting in-depth patient interviews to explore these factors.
Our work is consistent with others showing adherence with ULDs is generally poor, ranging from 44% to 64% of the study populations [8
]. Previous studies also confirm our finding that younger age is associated with non-adherence [8
]. Interestingly adherence was best in gout patients in the middle age groups (ages 55 to 64). This finding has been seen in the medication management of other chronic conditions, such as diabetes [20
This study adds to the body of knowledge regarding non-adherence in the management in gout. First of all, we evaluated adherence in new users of ULDs and included a sample of gout patients that reflects the typical outpatient medical practice. In addition, we evaluated measures of gout care that have not been previously examined including number of physician encounters for gout prior to ULD initiation. Lack of provider visits associated with a gout diagnosis prior to ULD initiation was associated with non-adherence. This suggests a face-to-face meeting focused on gout is needed to discuss the rationale and goals of medication treatment of gout. Interestingly, we found that 7% of our population had no encounters prior to initiating ULDs. We surmise this occurred when patients called the physician's office for a prescription before a visit could occur. Since these patients may not be new users but rather patients with a long gap since their last prescription, we conducted a subanalysis excluding those patients from the model. Non-adherence was still associated with younger age and fewer comorbid conditions.
Use of NSAIDs, a class of medications used to treat acute gout, prior to ULD initiation was also significantly associated with non-adherence and the relationship persisted even when we controlled for use of prophylactic medications prior to ULD initiation. This suggests that patients with likely inadequately controlled gout prior to ULD initiation (reflecting the need for prescription NSAIDs) are less adherent. This finding was contrary to our a priori hypothesis that active gout would be linked to higher adherence. Interestingly, lack of prophylactic medications (NSAIDs or colchicine dispensed in the 30 days prior to and including the date of ULD initiation) was not associated with non-adherence.
These results have practical implications for clinicians. While many providers assume patients with painful arthritic conditions are adherent to their medications, our work has shown that this is not the case. Providers and health care systems may wish to identify patients at high risk for non-adherence based on the factors identified in this study. In those high-risk subsets of the gout population, providers could emphasize the rationale and benefits of ULDs in the treatment of gout and the consequences of non-adherence. Of note, post hoc analyses revealed that fewer number of provider visits for gout following ULD initiation were also associated with greater non-adherence both in adjusted and non-adjusted analyses. In light of these data, providers may wish to automatically schedule follow-up encounters after ULD initiation to review clinical status and to encourage medication adherence.
One of the strengths of this study is the sample inclusion criterion of a diagnosis of gout, which other studies have not featured. While this does not eliminate misclassification bias, it does reduce the likelihood that patients were receiving ULDs for the treatment of asymptomatic hyperuricemia, in which treatment recommendations and goals may differ from the standard lifelong treatment of gout with ULDs [4
]. We also included data from two health delivery systems in different geographic regions, which reduced the influence of regional prescribing practices on our results and increased generalizability. Additionally, we were able to explore the relationship between gout-related care, such as provider visits for gout, use of acute gout medications prior to ULD initiation and use of potentially prophylactic medications. Lastly, given the study population had pharmacy benefits and ULDs are relatively inexpensive, we minimized the likelihood that financial constraints influenced adherence.
This study has several limitations. We conducted a retrospective analysis of pharmacy dispensings to measure adherence. Therefore, we could not confirm whether patients actually took the medications that they had filled. In addition, we did not have access to the patients or the clinical records to ascertain the reasons for gaps in therapy. We could not determine whether patients became non-adherent due to adverse reactions, at the suggestion of their provider, or secondary to other factors. However, it does seem less likely that non-adherence was due to an adverse reaction since when we re-ran the analyses excluding those who filled only one prescription the strengths of the associations were essentially the same.
Additionally, due to the limitations of pharmacy dispensing records we were not able to confirm the indication for NSAIDs and colchicine dispensed within the 30 days prior to and including the date of the first ULD dispensing. Patients may have also obtained over the counter NSAIDs that would not be captured by this study. However, since all the patients had pharmacy benefits, there is a financial incentive to obtain a prescription NSAID rather than take numerous over the counter pills to replicate the prescription dosage.
We did not have access to laboratory results and thus were unable to assess the impact of ULD adherence on uric acid levels. We also did not have access to the specialty of the ULD prescriber and thus could not examine whether adherence was influenced by provider specialty, specifically whether patients cared for by rheumatologists were more adherent. In addition, we were unable to determine definitely if visits associated with a diagnosis of gout were for acute gout flares versus routine follow-up appointments. Therefore, we could not directly determine the relationship between adherence and the frequency of gout attacks. Lastly, the population was overwhelming Caucasian, and thus we could not examine whether patient race and ethnicity influenced adherence.