We found that the risk of discontinuing octreotide was greater than lanreotide in this analysis of “real world” acromegaly data. The potential implications are important, since adherence and persistence are necessary for these drugs to work effectively. The use of the MarketScan database enables a longer-term assessment of adherence in a less structured setting vs clinical trials. Patients enrolled in the three trials that led to the approval of octreotide were treated for either 12 or 28 months (52 or 112 weeks) and patients enrolled in the clinical trials with lanreotide were treated for either 48 or 52 weeks [8, 9]. In this retrospective analysis, the median persistence for treatment was 169 days (5.6 months) with long-acting octreotide and 400 days (57.1 weeks) with lanreotide depot. Why treatment persistence was different between the two drugs in this setting is worth further exploration.
This analysis utilized the MarketScan database to retrospectively study the adherence and persistence of treatment with either lanreotide or octreotide in patients with acromegaly. While the initial data search included patients being treated with pegvisomant, a daily GH agonist, there were ultimately only 1308 patients identified who had been treated with a single SSA, with only 181 of these patients taking lanreotide over the 5.5-year data collection period before the analysis was limited with a washout period.
This analysis excluded patients who had received more than one therapy for treatment of acromegaly. It may be worth considering including these patients in future studies, particularly since this may help explain differences in adherence and persistence, such as reasons for discontinuing an SSA or starting a different one. The current analysis establishes a comparison of adherence and persistence in a set of patients who are likely receiving first-line therapy with an SSA due to the exclusion of more than one therapy and inclusion of a washout period. Using these methods for analysis of adherence and persistence with a more inclusive dataset would also be more reflective of actual clinical practice and increase the number of patients in the analysis.
The washout period was included in this analysis in order to minimize the likelihood of an effect of any SSA injections prior to the start of the data collection period. There is no standard length for a washout period with previous reimbursement claim analysis studies, which have used a 6-month or 12-month washout period [15, 16]. A longer washout period more effectively isolates treatment effects; however, this is at the cost of reducing the sample size. For this analysis, a washout period of 180 days was selected to improve data quality, which significantly decreased the sample size.
An interesting finding from this analysis was that the inclusion of a washout period altered the persistence or likelihood to discontinue treatment with a SSA in the absence of an effect on adherence. This effect was not on the adherence, the parameter more temporally related to the start of therapy and the potential influences of previous therapies. The effect of the washout was on how long patients remained on therapy. In this analysis, there was no difference in adherence, measured by MPR, between patients receiving lanreotide and octreotide regardless of the inclusion of a washout period. In contrast, the persistence of therapy with lanreotide and a decrease in the likelihood of discontinuing lanreotide was only observed when a 180-day washout was incorporated. Possible differences between lanreotide and octreotide that may impact adherence and long-term persistence include a subcutaneous route of administration for lanreotide, an intramuscular injection for octreotide, and the availability of lanreotide in a prefilled syringe compared with the need to dilute octreotide prior to injection [8, 9]. While these factors may confer a clinical advantage favoring lanreotide in some patients, it is not clear from the retrospective data analysis reported here that these factors would be important for differences in persistence of SSA therapy due to inclusion of a washout period. The reason for this washout-associated difference in persistence should be explored. Further, addition of clinical information about reasons for discontinuation of therapy, any further therapy the patients who discontinue therapy with an SSA may receive, and persistence to the second therapy may be useful for clinicians as they chose an initial and second therapy for their patients.
When determining the clinical impact of this analysis, the primary limitations include the number of patients included in the analysis, the exclusion of patients who had switched therapy, and the lack of clinical data from these patients. Acromegaly is a rare disease, and the analysis of the database over a 5.5 year period only captured 1,308 patients who had received a single SSA. The number of covered lives in the database was not available, but the number is less than what would be expected based on the incidence and prevalence of the disease. Possible explanations for the lower number of prescriptions on average may be that patients changed medical plans or medical plans stopped reporting data to Truven. The use of the 180-day washout period and the exclusion of patients who switched therapies contributed to the low accrual. The combination of adherence and persistence data with clinical information may lead to interesting findings impacting the use of each SSA if drug toxicity or a lack of response lead to decreased adherence and persistence due to a need to change therapy. Finally, inclusion of clinical data, particularly at the time that drug was discontinued, could provide very important information to understand the finding of this analysis. In these patients, the adherence was not significantly different for the two drugs and this likely reflects similar tolerance. In the absence of clinical data, it is unclear if the increased persistence is good or bad. A shorter persistence on therapy with octreotide due to toxicity would be favorable for use of lanreotide, while a longer persistence on lanreotide due to less effectiveness to control the acromegaly would support use of octreotide. The incorporation of clinical data would answer these questions. Otherwise, the persistence is longer in patients receiving lanreotide in the setting of a washout period, but while the clinical impact can be inferred, it isn’t clear.
This analysis was a by-product of a market share analysis so the octreotide and lanreotide patients could not be directly compared. Without the addition of a matching step using propensity scores, it could only be assumed that the octreotide and lanreotide treatment groups were comparable. Because we identified patients by diagnosis codes and treatments, there was no indication of whether the patients were on extended schedules or in withdrawal in the claim database. There was no evidence the extended schedule or withdrawal period were happening disproportionally between two treatment groups. Therefore, we did not stratify on that variable, which may be a potential confounder in the interpretation of the results.