Adherence to antimuscarinics in children with overactive bladder

Abstract

Objectives:

Adherence to antimuscarinics for the treatment of overactive bladder is known to be low in adults but there is scarce data on adherence in paediatric patients. Our objectives were to evaluate the adherence of children to antimuscarinics and to identify influencing factors.

Methods:

Children aged 5 to 18 years and treated with an antimuscarinic agent for at least 6 months were recruited at a routine visit and had to fill out a questionnaire. Their pharmacists were then contacted to inquire about prescription renewals since the beginning of treatment. The medication possession ratio was calculated and grouped by time blocks of 1, 3, 6 and 12 months. The pharmacists were contacted again 6 months after the recruitment visit. A medication possession ratio ≥ 80% was considered as good adherence.

Results:

Seventy-two patients were recruited with a mean age of 10.1 years. The self-reported adherence was 93%. Prior to the questionnaire, the medication possession ratio was ≥ 80% in 36%, 57%, 64% and 74% of cases in blocks of 1, 3, 6 and 12 months, respectively. After the questionnaire, the medication possession ratio improved to 53%, 65% and 71% for blocks of 1, 3 and 6 months, respectively. No influencing factors were identified.

Conclusions:

Measured adherence to antimuscarinics in children with overactive bladder is higher than in adults but significantly lower than the self-reported adherence. Good self-reported adherence must be questioned to avoid unnecessary dose escalation or change of medication. Strategies to increase medication adherence are required to improve treatment efficacy.

As defined by the International Children’s Continence Society, overactive bladder (OAB) is ‘urinary urgency, usually accompanied by frequency and nocturia, with or without urinary incontinence, in the absence of urinary tract infection or other obvious pathology’. (1) OAB is a highly frequent disease in adults, with prevalence rates ranging from 14% to 28% (2–4). Its prevalence in the paediatric population has been minimally studied but one epidemiological study reported a 17.8% prevalence rate in children (5). OAB has been shown to have a detrimental impact on quality of life in numerous studies (4,6–9) and improvement of quality of life is obviously one of the main goals of treatment of this condition. The main treatment options for OAB include behavioural therapy and pharmacotherapy, with either an antimuscarinic agent or a β₃-adrenoceptor agonist. More invasive treatment modalities are reserved for severe or refractory cases.

Poor adherence to medication represents a major challenge in the management of any disease. Adherence has been reported to be very low in the adult population treated with antimuscarinic medications. For example, in 2013, Sicras-Mainar et al. reported adherence rates at 12 months of 35.8%, 31.9% and 30.9% for fesoterodine, solifenacin and tolterodine, respectively (10). Likewise, other studies have reported that solely 14% (11) and 30% (12) of their population were more than 80% adherent to their antimuscarinic medication. Balkrishnan et al. stated that the medication possession ratio (MPR) of their population across 3 years was 42% (13). Adherence to antimuscarinic medications has been reported as drastically higher in clinical trials than what is reported in clinical practice, often superior to 80%, most likely because those trials are of short duration and are designed for patients to be intensively followed and monitored (14). To our knowledge, there is currently no data on adherence to antimuscarinics for the treatment of OAB in the paediatric literature.

There are several methods for measuring adherence to drug therapy, including self-report, return of unused medications by the patient, retrospective review of pharmacy notes, MPR, electronic medications monitors, medication weight and biological assays (14). The MPR is defined as the number of days of medication dispensed within the refill interval divided by the number of days between prescription refills (14). It has the advantage of obtaining real life situation data without influencing patients’ behaviour but its use implies assuming that patients are properly taking the medication when it might not always be the case.

Our primary objective was to evaluate the adherence of children with OAB treated with antimuscarinic medications and our secondary objective was to assess factors that could possibly be influencing adherence.

METHODS

Study population

Patients were eligible for the study if they were aged between 5 and 18 years, had been diagnosed with OAB by a paediatric urologist, and had been taking an antimuscarinic medication for at least 6 months. Patients (or parents) unable to understand French or to complete the questionnaire were excluded from the study. Patients were recruited by the paediatric urologist at the end of a routine follow-up visit if they met the inclusion criteria.

Study design

We performed an 8-month, monocentric, interventional study with retrospective and prospective components. After recruitment, patients and their families were given a starting package including an information leaflet on the study, consent forms to participate in the study and to allow a team member to contact their pharmacist, and a questionnaire to collect demographic data and self-reported adherence. In our experience with the paediatric population, adherence is most often reported by a parent (proxy-reported adherence) than by the child himself. However, we did not distinguish these two types of adherence in our study population and will use the term ‘self-reported adherence’ in the remainder of this paper. Medical records were reviewed to collect data on antimuscarinic medication regimen, side effects and concomitant use of other medications.

After written consent was obtained, a team member other than a urologist contacted the patient’s pharmacist and inquired about the patient’s adherence to his or her antimuscarinic medication. Adherence to antimuscarinic medications was measured using the MPR. A MPR ≥ 80% was considered as good adherence (11,12,15). Prerecruitment MPRs were grouped in blocks of 1, 3, 6 and 12 months to limit potential bias related to monthly fluctuations in adherence pattern. For example, if a child gets a new medication bottle prior to the end of his renewal period because of convenience, he would appear to be extremely adherent for this particular month but he would then appear to be poorly adherent the following month since he has more than a full bottle to finish before the next renewal. Grouping the MPRs in time blocks might therefore attenuate this possible bias. Urologists were blinded to adherence data to avoid influencing their management plan and their relationship with their patients. Follow-up visits were scheduled routinely according to the urologists’ treatment plan and were not influenced by data obtained from the questionnaire or the pharmacist. MPRs were again obtained through the pharmacists 6 months after recruitment to evaluate the potential change in adherence after the administration of the questionnaire and were again grouped in blocks of 1, 3 and 6 months.

This study was approved by our Institutional Review Board and was conducted from November 1, 2013 to July 1, 2014 and postquestionnaire MPR was obtained up to February 2015.

Statistical analysis

The McNemar test was used to evaluate medication adherence before and after the recruitment visit and administration of the questionnaire. The chi-square test was used to compare medication adherence to categorical patients’ characteristics. A P value less than 0.05 was considered statistically significant.

RESULTS

Baseline data

Seventy-five patients were recruited for the study but three had to be excluded because they either did not speak French adequately to answer the questionnaire or were unable to properly answer the questionnaire. Seventy-two patients (24 girls, 48 boys) were therefore enrolled in the study, with a mean age of 10.1 ± 3.2 years and a mean duration of antimuscarinics use of 29 months (95% CI 22 to 35) at the time of questionnaire completion. Patients were using solifenacin in 80.6% (n=58) of cases, while 25.0% of patients (n=18) were using oxybutynin, 6.9% (n=5) were using tolterodine and 8.3% (n=6) were using other antimuscarinics. Almost all children were using a long acting molecule (94.4%). The majority of patients (76.4%) were living with both of their parents, while 11.1% were living with only one parent and 9.9% were in shared custody. The highest level of education completed by either of the parents was high school in 34.5%, college in 27.4% and university in 30.9%. Fifty-four per cent of the children were supervised by both of their parents in the taking of their medication, while 43.1% had supervision by only one parent. Dry mouth (25.0%) and constipation (18.1%) were the most frequently reported side effects. Forty-two per cent of the patients were taking at least one other daily medication in addition to their antimuscarinic.

Adherence

The pre-recruitment self-reported adherence was 93 ± 10% with an average of 0.5 ± 0.9 doses of medication forgotten per week. Overall, 2722 prescription refill periods were evaluated. As indicated in Table 1, prior to the recruitment visit and completion of the questionnaire, the MPR was over 80% for 36%, 57%, 64% and 74% of patients for blocks of 1, 3, 6 and 12 months, respectively. Follow-up after completion of the questionnaire revealed that the MPR was over 80% for 53%, 65% and 71% of patients for blocks of 1, 3 and 6 months, respectively. The improvement in MPR for 1-month blocks was statistically significant (P=0.01). Although there was no statistical significance noticed when comparing blocks of 3 and 6 months, a trend could be observed. It therefore appears that the recruitment visit and administration of a questionnaire might have had a positive impact on medication adherence.

Table 1.

Adherence to antimuscarinics per different time blocks in children with overactive bladder before and after a recruitment visit

Time blocks (in months)	Patients with MPR* ≥ 80%				P value
	Prerecruitment		Postrecruitment
	n	%	n	%
1	26	36.1	38	52.8	0.01
3	41	56.9	47	65.3	0.06
6	46	63.9	51	70.8	0.12
12	53	73.6

*MPR Medication possession ratio

We could not identify any factors significantly influencing adherence to antimuscarinic medications in children with OAB (Table 2).

Table 2.

Factors that may influence antimuscarinic adherence in children with overactive bladder

Factors		MPR* ≥ 80% per 6-month blocks	P value
		%
Sex	Girls	56.5	0.34
	Boys	68.1
Family status	Living with both parents	70.4	0.10
	Shared custody	57.1
Adults supervising medication	1	64.5	0.57
	2	63.2
Medication	Oxybutynin	64.7	0.99
	Tolterodine	80.0	0.46
	Solifenacin	63.2	0.56
Medication formulation	Short acting	75.0	0.18
	Long acting	64.2
Dry mouth	Yes	72.2	0.44
	No	62.3
Constipation	Yes	76.9	0.31
	No	62.1
Using another medication	Yes	72.4	0.26
	No	59.5

*MPR Medication possession ratio

DISCUSSION

This is the first study evaluating adherence to antimuscarinic medications in children with OAB. Although the adherence measured with the use of MPR was significantly different than the self-reported adherence, it was still appreciably higher than in the adult population. Indeed, 74% of children had a MPR of at least 80% in the 12-month block prior to being recruited in the study. The notable difference between self-reported adherence in the paediatric and adult populations might be due to the fact that self-reported adherence in children is often actually a proxy-reported adherence and that parents might tend to inflate their children’s adherence rate to prove that they have strong parenting skills and are reliable for their children’s medical care.

Adherence appeared to be improved after the recruitment visit and administration of the questionnaire, although this was statistically significant solely for 1-month time blocks. Although oxybutynin is currently the only antimuscarinic approved for the treatment of OAB in children in North America, solifenacin was the most commonly used antimuscarinic in our study population (80.6%), mainly because of our centre’s previous experience in children with this molecule (16,17). No factors influencing adherence were identified in this study.

The fact that there was a noticeable discrepancy between the measured and self-reported adherence raises concern. Indeed, one must thoroughly question self-reported good adherence in order to avoid unnecessary dose escalation or change of medication, as well as invasive investigations, which might not be required for treatment efficacy and might engender or worsen side effects or increase health care costs (14). In 2006, Balkrischnan et al. showed that better adherence, or increased MPR, was the strongest predictor in the reduction of health care costs, with a 10% improvement in MPR associated with a 6% decrease in associated costs (13). The World Health Organization has recognized treatment adherence as a primary determinant of treatment success and that suboptimal adherence to medication could lead to increased health care costs, morbidity and even mortality (18).

In virtually all studies on medication adherence or persistence, reasons for poor adherence or for complete discontinuation are similar. The most frequently cited explanation is poor efficacy or that the medication did not work as expected (19–23). The presence of side effects is usually the second most common reason for discontinuation (20–22,24). It has been shown that counselling patients at the start of therapy significantly improves their adherence to medication (14). Indeed, it is important to discuss realistic expectations about treatment efficacy and to advise patients about possible side effects of their medication in order to avoid discontinuation due to misinformation. Moreover, we routinely ask our patients about their adherence rate and request a minimum rate of 80% before making changes in their medication regimen. Side effects are also assessed at every visit and any associated constipation is aggressively treated. Other possible reasons for discontinuation are the high cost of medications (19,21), the lack of insurance coverage for medication (21) or that the patients learned to get by without the medications (21).

It has been suggested that long acting medications would be better adhered to than short acting medications that need to be taken at least twice a day (25,26) but this has not been supported by our data. However, this could be explained by the fact that we had a very minimal number of children on short acting medication (n=4) and therefore not enough patients to reach a valid conclusion. In clinical practice, we try to switch our patients to long acting formulations as soon as they can swallow pills in order to facilitate adherence since taking medication during the daytime might be difficult, especially during school hours in elementary school.

Finally, limitations of this study of course include its partially retrospective nature. However, the retrospective portion was essential to obtain a real life evaluation of adherence prior to enrolling patients in the study and therefore possibly changing their behaviour toward adherence. The main disadvantage of using MPR to assess medication adherence is the possibility of overestimating results, as an assumption is made that the amount of medication dispensed will perfectly correlate with the amount of medication actually consumed, which is definitely not likely to be the case (14). Likewise, the shortcoming of using self-reported adherence is that patients tend to overestimate their adherence regimen to please their physicians (14). Therefore, the measured and self-reported adherence rates mentioned in this study are most likely overestimated. Moreover, the fact that the questionnaire was completed right after a urology visit might have influenced patients’ and parents’ answers. However, in comparison to using a mailed questionnaire where more adherent patients might be more inclined to participate in the study, having the patients complete the questionnaire in the clinic meant that almost every patient asked to participate in the study did provide consent; this might therefore have limited a potential selection bias.

CONCLUSION

Adherence to antimuscarinics in children with OAB is higher than in adults but still far from perfect. Poor medication adherence is a significant problem despite close medical monitoring because it contributes to suboptimal treatment efficacy and therefore lessens the improvement in quality of life associated with treatment success. Effective strategies are consequently required to increase adherence to medication. Having patients fill out a questionnaire assessing adherence and telling them that their adherence will be monitored might be a useful intervention, although our data did not clearly prove its sustained efficacy. Therefore, the use of such questionnaires needs to be more thoroughly studied. Similarly, factors correlating with poorer adherence need to be identified in future trials to target the groups of patients that would most likely benefit from an intervention. The results of this study are perhaps comparable to medication adherence in children with other chronic diseases.