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PRIORITY PRESS - 74th Annual Scientific Meeting of the American College of Gastroenterology

San Diego, California / October 23-28, 2009

Patients with chronic conditions such as ulcerative colitis (UC) usually have to take medication throughout their lives. As a result, persistence with therapy has an especially prominent role in treatment success and in clinical decision-making. Simplicity, tolerability and efficacy of a treatment regimen for UC all affect the likelihood that a patient will remain adherent to the regimen.

Understanding patient-specific factors that influence persistence with therapy can help clinicians individualize therapy to maximize adherence.

“Persistence in therapy for any chronic illness is a clinically relevant issue,” stated Dr. Sunanda Kane, Mayo Clinic, Rochester, Minnesota. “We are just now understanding that being persistent is just as important as being ‘compliant,’ as it is the long-term effect of therapy to control disease that can improve outcomes.”

Database Analysis

To examine patient persistence among 5-aminosalicylic acid (5-ASA) agents, Dr. Kane and colleagues analyzed prescription records from a large US pharmacy database. Patients whose records showed a new prescription for 5-ASA between March and September 2007 were included in the analysis. Investigators followed persistence over an 18-month period for the following 5-ASA formulations: delayed-release (DR) 800 mg; balsalazide (generic and non-generic); olsalazine; multimatrix delivery (MMX); and 250 and 500 mg DR. Patients of any age were included if they had a new prescription for oral 5-ASA therapy filled during the period reviewed. Patients were considered persistent after three months of continuous therapy, and investigators examined refill records of all persistent patients at 12 and 18 months.

On the basis of prescription refill activity, patients were classified monthly as continuing, restarting, switching, titrating, discontinuing or no activity. Only patients classified as continuing or restarting were included in the analysis. Continuing was defined as refilling a prescription within a timeframe of up to twice the duration of the prescription. For example, if the initial prescription was for 30 days, a patient who refilled the prescription within 60 days was continuing with therapy. Restarting categorized patients who refilled a prescription at some point after twice the duration of the prescription.

The analysis included 19,398 patients who were classified as “continuing” after three months. The total comprised 10,727 patients using 800 mg DR, 1972 using balsalazide, 126 using olsalazine, 3687 using MMX, 555 using 250 mg DR and 2331 using 500 mg DR.

Differences in Persistence

Fewer than half of the patients who were continuing at three months remained persistent at 12 months. Persistence rates continued to decline between 12 and 18 months. At both time points, MMX had the highest rate of persistence, 34% at 12 months and 22% at 18 months. Persistence rates at 12 months were lower still among patients classified as “restarting,” ranging from 7% to 13%. “However, patients who did restart their medication during this study appeared to maintain persistence until the 18-month follow-up,” Dr. Kane and colleagues reported. “Patients prescribed MMX were more persistent with their medication than patients prescribed other mesalamine formulations.”

During the 18 months of follow-up, patients taking the MMX formulation accumulated an average of 250 days of therapy and 7.89 prescriptions, both of which were significantly higher than for any of the other 5-ASA formulations (P<0.05). “These findings may reflect the once-daily dosing, lower pill burden or greater patient satisfaction with MMX compared with other formulations,” the investigators concluded.

Assessment by Gender, Age and Physician Specialty

Two related analyses of the same database provided insights into factors associated with persistence among patients with UC treated with mesalamine. In one analysis, Dr. Kane and colleagues examined factors that influenced persistence at three, 12 and 18 months. They reviewed claims records for 44,191 patients who filled a prescription for one of the previously described formulations of mesalamine.

Patients who started treatment with MMX had the highest rates of persistence at all three time points (60% at three months, 20% at 12 months and 13% at 18 months). Investigators evaluated the effect of patient age and sex and the specialty of the prescribing physician on persistence. For all formulations, of mesalamine, men had higher persistence rates than did women. Moreover, men were more persistent than women at all three time points.

With respect to age, the highest persistence rates were observed in patients aged 41 to 55 years. Persistence rates in that age group ranged from 62% to 36% at three months, 21% to 8% at 12 months and 15% to 5% at 18 months. At each time point, patients treated with MMX had the highest rates of persistence.

Analysis of the data by physician specialty showed that persistence rates were highest for patients of gastroenterologists and internists at all three time points and for all formulations except the 250 mg/500 mg DR formulation, which had the highest persistence rates among patients of gastroenterologists and other types of surgeons. Patients prescribed MMX had the highest persistence rates at three months (60% to 61%), 12 months (21% to 22%) and 18 months (14%).

Long-term Outcomes

A third analysis focused on factors associated with long-term persistence with mesalamine therapy in the cohort of 44,191 patients. Dr. Kane and colleagues examined records of patients who were persistent at 12 months and compared the findings with those from an examination of records at 18 months.

The analysis revealed that 4776 patients were persistent with therapy at 12 months: 2384 with 800 mg DR, 445 with balsalazide, 36 with olsalazine, 1247 with MMX, 542 with 500 mg DR and 122 with 250 mg DR. A majority of patients who were persistent at 12 months remained persistent at 18 months for all formulations of mesalamine except 250 mg DR (49%).

Patients who were persistent at 12 months were most likely to be persistent at 18 months when treated with MMX (66%) compared with the other formulations (56% to 59%). After 18 months of treatment, patients who were prescribed MMX had received an average of 162 days of therapy and an average of more than five prescriptions. These results were significantly more than those in the largest treatment group, i.e. the patients on 5-ASA 800 mg DR.

The investigators concluded that the data “indicate that many patients who are persistent for 12 months are likely to remain so. Further research is needed to devise strategies that encourage patients to be adherent and persistent with their 5-ASA therapy.”

Collectively, the three analyses show that “5-ASAs, to maintain remission, are safe and effective, and that those patients who are persistent have overall lower healthcare costs and better outcomes,” Dr. Kane told delegates. “The take-home message is that it appears that the more simple you can make a regimen, the better the persistence. However, there are multiple factors involved with persistence and healthcare providers have to be aware that making medications once a day is not the simple fix.”

Treatment Adherence of Patients with Crohn’s Disease

An unrelated analysis reported by Dr. Kane showed that adherence influences outcomes for other classes of therapy for inflammatory bowel disease. The study involved 749 patients with Crohn’s disease treated with the biologic agent adalimumab.

Investigators examined associations between adherence to maintenance therapy with the biologic agent and rates of hospitalization and associated healthcare costs. They defined “maintenance” as no gap in prescription more than four weeks during the first 12 weeks of therapy and at least one refill after 12 weeks. Adherence was defined in terms of medication possession ratio (MPR: total days of supply of therapy/duration of study period). Patients with an MPR of 0.8 or higher were considered adherent.

The results showed that adherence during the first six months of therapy was associated with significantly lower rates of hospitalization for all causes and for Crohn’s disease, significantly lower rates of emergency department visits and significantly lower healthcare costs for any reason, and specifically for Crohn’s disease (P=0.03 to P<0.01).