Subcutaneous buprenorpine rivals sublingual for opioid use disorder

 

Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.

Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.

In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.

The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.

Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.

Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.

After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting. The response rates for the subcutaneous buprenorphine depot and sublingual buprenorphine with naloxone groups were 17% and 14%, respectively.

 

Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.

As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.

The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.

“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.

The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.

SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.

 

Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.

Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.

In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.

The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.

Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.

Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.

After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting. The response rates for the subcutaneous buprenorphine depot and sublingual buprenorphine with naloxone groups were 17% and 14%, respectively.

 

Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.

As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.

The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.

“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.

The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.

SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.

 

Long-acting subcutaneous doses of buprenorphine depot are an effective treatment option for opioid use disorder, results of a phase 3 study of 428 adults show.

Sublingual buprenorphine hydrochloride is a standard treatment for opioid use disorder (OUD), but challenges include poor medication adherence, potential for abuse, and accidental exposure to children, Michelle R. Lofwall, MD, of the University of Kentucky, Lexington, and her colleagues reported.

In a study published in JAMA Internal Medicine, Dr. Lofwall and her associates randomized treatment-seeking adults with moderate to severe opioid use disorder to subcutaneous buprenorphine depot weekly for 12 weeks followed by monthly for 12 weeks, or daily sublingual buprenorphine with naloxone for 24 weeks.

The proportion of opioid-negative urine samples was 35% in the subcutaneous buprenorphine depot group (1,347 of 3,834 samples) vs. 29% in the sublingual buprenorphine with naloxone group (1,099 of 3,870 samples) for a statistically significant difference of 6.7%. Urine samples were collected weekly for the first 12 weeks, and then at weeks 16, 20, and 24, reported Dr. Lofall, a psychiatrist and addiction medicine specialist, and her associates.

Patients in the sublingual buprenorphine with naloxone group received 4 mg of sublingual buprenorphine hydrochloride and naloxone hydrochloride at the start of the study, titrated to 16 mg/day. The average treatment dosage was 18-20 mg/day for sublingual buprenorphine with naloxone patients.

Patients in the subcutaneous buprenorphine depot group received 16 mg of subcutaneous buprenorphine in a weekly injection at the start of the study; monthly subcutaneous buprenorphine depot injections were 64, 96, 128, or 160 mg between weeks 12 and 24.

After initial titration, doses were flexible based on clinical judgment, the researchers noted, similar to the way in which patients would be managed in a clinical setting. The response rates for the subcutaneous buprenorphine depot and sublingual buprenorphine with naloxone groups were 17% and 14%, respectively.

 

Adverse events were similar between the groups. The most common were injection-site pain, headache, constipation, nausea, and injection-site pruritus and erythema. Injection-site reactions were mild to moderate.

As a secondary outcome, the cumulative distribution function (CDF) in the subcutaneous buprenorphine depot group was statistically superior to the CDF found in the sublingual buprenorphine with naloxone in the percentage of opioid-negative results. “Cumulative distribution function values are an established endpoint used in early placebo-controlled, phase 3 clinical trials for OUD treatment,” Dr. Lofall and her associates wrote.

The study findings were limited by several factors, including an absence of assessment of patient adherence to sublingual medication and an inability to assess effectiveness vs. efficacy. However, the large size and diverse study population strengthen the results, which support the use of subcutaneous depot buprenorphine formulations for patients with OUD, the researchers noted.

“These formulations may also address potential limitations and concerns about daily dosing, including diversion, misuse, and accidental exposure of medication to children,” they said.

The study was supported in part by Braeburn Pharmaceuticals and the University of Kentucky, Lexington. Dr. Lofwall disclosed research funding and consulting fees from Braeburn Pharmaceuticals and Indivior.

SOURCE: Lofwall M et al. JAMA Intern Med. 2018 May 14. doi: 10.1001/jamainternmed.2018.1052.