Poster Number-8 - Differences in the severity of medical outcomes of exposures reported to poison centers involving XTAMPZA® ER and other opioid analgesics

Opioids are a frequently used treatment for acute and chronic pain in the United States. Misuse of these medications is also common and places the individual at significant risk of overdose and death. The development of abuse deterrent formulations (ADFs) is one approach prioritized by the U.S. Food and Drug Administration (FDA) to reduce the harms of prescription opioid misuse. In a guidance to pharmaceutical manufacturers, the FDA outlined four categories for evaluating the effectiveness of ADFs with the fourth category being demonstrated reduced abuse, misuse, and related adverse outcomes such as overdose and death in the post-approval, real-world setting.  As of 2022, no opioid has met category four labeling requirements.  XTAMPZA® ER (Collegium Pharmaceutical, Stoughton, MA) is an oxycodone analgesic with properties intended to discourage tampering. XTAMPZA ER was granted abuse-deterrent labeling with respect to oral, nasal and intravenous routes of administration based on premarket studies. It was first dispensed to patients in 2016.  Post-marketing studies of XTAMPZA ER are consistent with the aim of reduced abuse and tampering. However, it is unclear whether these changes correspond with meaningful reductions in adverse outcomes associated with misuse and abuse such as overdose and death. Poison centers are a useful data source to assess medical outcomes such as overdose and death related to misuse of pharmaceuticals. We assessed the number of XTAMPZA ER exposures reported to poison centers and whether they are less likely to be classified as intentional (e.g. abuse, misuse, or suspected suicidal) than exposures involving other opioid analgesics. We examined whether the severity of outcomes for exposures involving XTAMPZA ER were less severe than exposures involving other opioids. Finally, we assessed whether XTAMPZA ER corresponded to less severe outcomes among intentional exposures.

Methods:

Data collected between 1^st quarter 2016 through 4^th quarter 2021 from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System Poison Center Program were used. Data from cases involving 1) XTAMPZA ER, 2) immediate-release (IR) single-entity (SE) oxycodone 3) other ADF extended-release (ER) opioids, 4) non-ADF ER opioids 5) unspecified oxycodone, and 6) unspecified morphine were analyzed. Analyses were restricted to cases where the exposure was followed to a known outcome of either no effect, minor effect, moderate effect, major effect, or death and to instances where the route of administration was known to involve ingestion, inhalation, or injection.  Multinomial logistic regression was used to compare the proportion of XTAMPZA ER exposures that were either abuse/misuse/unknown or suspected suicidal to other opioids. Medical outcome was treated as an ordinal variable, from no effect to death. We compared medical outcome of XTAMPZA ER to other drug groups for all exposures and for intentional exposures. To compare severity of medical outcome between drug groups we used nonparametric Kruskal-Wallis test. If there was a statistically significant difference between drug groups based on the Kruskal-Wallis test, we conducted the Dunn test  to compare differences between XTAMPZA ER to each comparator. Multiple comparisons were adjusted for using the false discovery rate.  A lower mean rank of medical outcomes was interpreted as cases being less severe on average than comparator groups.

Results: From 2016 through 2021 there were 161 exposures involving XTAMPZA ER that were followed to a known outcome. Of these, 16 (9.9%) were intentional misuse/abuse/unknown exposures, and 47 (29.2%) were suspected suicidal exposures. The percentage of XTAMPZA ER  exposures that were either abuse/misuse/unknown or suspected suicidal were statistically significantly less than for other drug groups. We compared the distribution of medical outcomes within each drug group. The results of the Kruskal-Wallis test indicated a statistically significant difference in the distribution of medical outcomes (Χ²=350.80,  df=5, p< 0.001). Results of the Dunn Test showed that the rank order for XTAMPZA ER was significantly lower than other drug groups, indicating that, on average, a case involving XTAMPZA ER is likely to be a less severe outcome relative to other comparators.  We examined whether intentional exposures involving XTAMPZA ER were less likely to result in severe outcomes than comparators. Results of the Kruskal-Wallis test were statistically significant (Χ2=15.2,  df=5,  p=0.010), but XTAMPZA ER values were not statistically significantly different from any comparator based on the Dunn test.

Conclusion:

We observed that a smaller percentage of XTAMPZA ER exposures reported to poison centers are categorized as either intentional misuse/abuse/unknown intentional or suspected suicidal compared to other opioids. Both the lower number of intentional exposures and lack of manipulation may explain the lower severity of medical outcomes for XTAMPZA ER across all exposures. Among intentional exposures involving XTAMPZA ER, no differences relative to other opioids were observed. For all drug groups, most intentional exposures involved multiple substances or the intent was self-harm.  In these instances, XTAMPZA ER outcomes were no different than comparators, though no formal statistical tests were conducted. Overall, these findings are consistent with reduced abuse related outcomes in the post marketing setting. However, additional efforts are needed to reduce the burden of prescription opioid misuse, including effective identification and treatment of mental health conditions, increased naloxone access, and treatment for polysubstance use disorders.

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