Patient adherence decreased with addition of second drug

Glaucoma specialists should consider the patient’s adherence to one drug before adding another, researchers suggest.

ByJeanne Gonzalez

Alan L. Robin

The addition of a second drug to a glaucoma patient’s medication regimen tends to increase the time it takes the patient to refill the original drug prescription, according to a recent study. The lag time in getting the drug prescription refilled — more than 2 weeks’ delay in almost one-fifth of cases, according to the study authors — may mean the patient is not taking the medications properly or is taking only one of the drugs.

Physicians often speak about glaucoma patients’ compliance — how the patient follows instructions. A better term, said Alan L. Robin, MD, and study co-author David Covert, MBA, may be “adherence,” a term that describes how well the patient voluntarily collaborates in a therapeutic course of behavior to produce a therapeutic result.

Adherence is often overestimated by physicians, according to the study authors. They conducted a retrospective review to track the drug refill interval of glaucoma patients after a second drug was added to their medication regimen.

“I noted that many older people don’t like to bother others for help,” Dr. Robin said in an e-mail interview. “They like to stay self-sufficient. It made me wonder if this could be a form of nonadherence. I often see patients who run out of one medicine, but take the others and don’t feel this is bad at all. [They] never wonder why all the medicines were prescribed.”

Dr. Robin said that in his own practice, if a patient is not adhering to a single drug regimen, he does not prescribe a second one. Rather, he replaces that initial drug with a more potent one or with a combination. In addition, he tries to increase his communication with the nonadherent patient and also tries alternate methods of communicating, he said.

Looking at adherence

Dr. Robin and Mr. Covert focused their study on the refill rate of latanoprost as a first-line drug, reviewing the records of the patients of a large national health care provider. Latanoprost was chosen because it was the medication most commonly used during the time of the study (July 2001 to June 2002), and it had only one bottle size. The researchers focused only on the refill rate of latanoprost alone; they did not evaluate its efficacy, other systemic medications or the progression of glaucoma in the patient cohort.

During the study period, 1,784 patients had a second medication added, and 3,146 patients remained on latanoprost monotherapy.

The researchers calculated the mean number of days it took each patient to refill their latanoprost prescription before and after the second drug was added. They also averaged the refill time for the second drug.

“We found a decrease in adherence associated with the addition of another therapy, irrespective of the [bottle] size, frequency of administration or class of adjunctive medication,” the authors said in their report on the study, recently published in Ophthalmology.

Refill lag time

The mean refill interval for latanoprost was 40.6 ± 21.8 days before the second drug was added and 47.4 ± 24.4 days after the addition, Dr. Robin said. The mean interval increased by 6.7 ± 25.6 days (95% confidence interval; range, 5.6 to 7.9 days; P < 0.001) after the second drug was added.

The study was not designed to find what percentage of patients adhered to the first drug, Dr. Robin explained, although it appeared that most patients had good adherence.

About one-third of the patients (602 of 1,784) refilled the latanoprost at the same interval or in less time after the addition of the second drug than before. Forty-three percent (773 of 1,784) refilled the prescription within 2 weeks of their initial refill time, Dr. Robin said.

But for 22.9% (409/1,784) of patients, the refill time increased by more than 2 weeks (P < 0.0001), he said.

“A similar distribution of refill intervals was seen when stratified by fill size or second-line drug,” the authors said in the study.

Refill times for latanoprost varied depending on what second-line drug was added and what size the bottle was, the researchers found. Among the secondary drugs added during the study were betaxolol, brimonidine, dorzolamide, a dorzolamide-timolol combination, levobunolol and timolol.

The refill times for latanoprost were similar or the same for the 3,146 patients who remained on latanoprost alone during the study (41 ± 24 days), he said.

Potential reasons for delay

The researchers said that, assuming the 2.5-mL latanoprost bottle yielded 25-µL drops, the bottle should have lasted 7 weeks. A delay of 2 weeks in the refill schedule might mean the patients were taking only one of the two medications their treatment required, Dr. Robin said.

He said some patients may believe that taking at least one of their prescribed medications suffices for their treatment.

Previous studies have shown that lack of adherence to a glaucoma medical regimen could lead to increased IOP and loss of visual field and visual function, Dr. Robin noted. Studies in which patients are electronically monitored have shown that patient adherence to drug regimens can be poor, he said.

“Improved adherence to medical therapy could result in considerable preservation of vision, as we have seen that lower IOPs are associated with less disease progression,” Dr. Robin said.

Adherence continues to be a difficult part of treatment to monitor, and the reason behind refill lag times remains unknown, he said. Physicians should consider the patient’s adherence to the first-line glaucoma drug regimen before adding a second drug, he suggested. They should also consider whether the patient is taking systemic medications because many patients have additional comorbid conditions, he said.

Dr. Robin noted that refilling glaucoma prescriptions on schedule does not indicate proper adherence to the drug regimen.

Consider total medication burden before adding glaucoma meds

Adherence to drug therapy regimens decreases as the regimen becomes more complex, noted Alan L. Robin, MD. Patients with glaucoma often have systemic comorbidities that involve multiple medications, and ophthalmologists should consider the total medication burden on their patients before prescribing additional medications, he said.

Dr. Robin and David Covert, MBA, performed a retrospective review of records from a 6-month clinical trial of glaucoma medications to assess the total burden of systemic medications on the patients in the trial. Hypertension and cholesterol were the two most common systemic comorbid disorders, the researchers said.

“Compliance is assumed to be related to complexity of therapy. Many subjects are also taking aspirin therapy, vitamins, calcium supplements and proton pump inhibitors,” the authors said in a poster presented at the American Glaucoma Society meeting.

Many studies of glaucoma therapies are conducted in patients who are otherwise healthy, and this does not reflect the true glaucoma population, the authors said. Patients with comorbid conditions are often excluded from trials, they said.

In the study population they examined, one-fourth of the patients required four or more medications with multiple doses per day, the authors said.

For Your Information:

Alan L. Robin, MD, can be reached at 6115 Falls Rd, Ste 333, Baltimore, MD 21209-2226 U.S.A.; +1-410-377-2422; fax: +1-410-377-7960; e-mail: glaucomaexpert@cs.com.

Reference:

Robin AL, Covert D. The systemic medication burden of glaucoma patients. Presented at: 15th Annual Meeting of the American Glaucoma Society; March 3-6, 2005; Snowbird, Utah.

For Your Information:

Alan L. Robin, MD, can be reached at 6115 Falls Road, Suite 333, Baltimore, MD 21209-2226 U.S.A.; +1-410-377-2422; fax: +1-410-377-7960; e-mail: glaucomaexpert@cs.com.

Reference:

Robin AL, Covert D. Does adjunctive glaucoma therapy affect adherence to the initial primary therapy? Ophthalmology. 2005;112:863-868.

Jeanne Michelle Gonzalez is an OSN Staff Writer who covers all aspects of ophthalmology, specializing in practice management, regulatory and legislative issues. She focuses geographically on Latin America.