OPIOID USE DISORDER

Open-label placebo for methadone treatment

Conditioned open-label placebo (C-OLP) may be an appropriate methadone treatment adjunct according to a paper published in JAMA Network Open.

In a two-arm, open-label, single-blind randomized clinical trial in an academically affiliated community opioid treatment program, 131 adults seeking treatment for moderate to severe opioid use disorder were randomized to either C-OLP (77, pharmacologic conditioning and a placebo pill and methadone) or treatment as usual (TAU; 54, methadone only).

The authors recorded no significant group differences in the mean 90-day methadone dose. However, the authors note that the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP. The C-OLP participants also reported significantly better sleep quality.

Reference: Belcher AM, Cole TO, Massey E, et al Effectiveness of conditioned open-label placebo with methadone in treatment of opioid use disorder. JAMA Netw Open. 2023;6(4). doi:10.1001/jamanetworkopen.2023.7099.

PAIN RELIEF

Medical cannabis may be complementary treatment

Medical cannabis (MC) may be a safe and effective complementary treatment for pain relief in patients with cancer, according to the authors of a paper published in BMJ Supportive & Palliative Care.

The authors analyzed data from 358 patients with cancer who were a part of the Quebec Cannabis Registry. They included Brief Pain Inventory (BPI), revised Edmonton Symptom Assessment System (ESAS-r) questionnaires, total medication burden (TMB), and morphine equivalent daily dose (MEDD) recorded at 3-month, 6-month, 9-month, and 12-month. Follow-ups were compared with baseline values.

Regarding adverse events, the authors write that 13 of 15 were not serious; 2 were serious: pneumonia and cardiovascular events but were considered unlikely related to MC.

Statistically significant decreases were observed at 3-, 6-, and 9-month follow-ups for BPI worst pain, average pain, overall pain severity, and pain interference.

ESAS-r pain scores decreased significantly at each follow-up period. Delta-9-tetrahydrocannabinol (THC): cannabidiol (CBD) balanced strains were associated with better pain relief as compared with THC-dominant and CBD-dominant strains. Decreases in TMB were observed at all follow-ups. Decreases in MEDD were observed at the first three follow-ups.

Reference: Aprikian S, Kasvis P, Vigano M, Hachem Y, Canac-Marquis M, Vigano A. Medical cannabis is effective for cancer-related pain: Quebec Cannabis Registry results. BMJ Support Palliat Care. [e-pub May 2, 2023]

C. DIFFICILE

Fecal transplant may decrease recurrent C. difficile infection

Fecal microbiota transplantation (FMT) can decrease recurrent Clostridioides difficile (C. difficile) infection (rCDI) compared with alternative treatments such as antibiotics, according to a paper published in the Cochrane Database of Systematic Review.

The authors reviewed randomized trials of adults or children with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C. difficile. They ultimately included 6 studies with a total of 320 participants.

The authors say all 6 studies showed a resolution in rCDI in FMT groups compared with controls. The authors speculate that FMT may reduce adverse events; however, confidence intervals (CIs) for this were wide. Similarly, the authors speculate that FMT may reduce all-cause mortality, but for this, the number of events was small, and CIs were again wide.

Reference: Minkoff NZ, Aslam S, Medina M, et al Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile). Cochrane Database Syst Rev. 2023;4(4):CD013871. doi:10.1002/14651858.cd013871.pub2.

CHEMOTHERAPY

Blinatumomab for infant therapy

Blinatumomab added to chemotherapy used in the Interfant-06 trial appeared to be safe and had a high level of efficacy in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia (ALL) compared with historical controls from the Interfant-06 trial, according to a paper published in the New England Journal of Medicine.

The authors observed the safety and efficacy of blinatumomab, a bispecific T-cell engager molecule targeting CD19, in infants with KMT2A-rearranged ALL. Thirty patients less than 1 year old with newly diagnosed KMT2A-rearranged ALL were given the chemotherapy used in the Interfant-06 trial with the addition of one postinduction course of blinatumomab.

The authors recorded no toxic effects, resulting in permanent discontinuation of blinatumomab or death, possibly or definitely attributable to blinatumomab. Serious adverse events included fever (4 events), infection (4), hypertension (1), and vomiting (1). Twenty-eight patients (93%) either were minimal residual disease (MRD)-negative (16 patients) or had low levels of MRD (12 patients) after the blinatumomab infusion.

All patients who continued chemotherapy became MRD-negative during further treatment. Two-year disease-free survival was 81.6%. Corresponding values for overall survival were 93.3% and 65.8%.

Reference: van der Sluis IM, de Lorenzo P, Kotecha RS, et al Blinatumomab added to chemotherapy in infant lymphoblastic leukemia. N Engl J Med. 2023;388(17):1572-1581. doi:10.1056/nejmoa2214171.

CANNABIS

Intentional, suspected suicidal cannabis exposures rise during pandemic

Intentional, suspected suicidal cannabis exposures reported to US poison centers increased from 2009 to 2021, according to a paper published in JAMA Network Open.

The authors reviewed data from the National Poison Data System for intentional, suspected suicidal cannabis exposures reported to US poison centers. They followed STROBE reporting guidelines and included closed cases of cannabis-related human exposures, age 5 years or older, with reason coded as intentional-suspected suicidal.

From 2009 to 2021, 18,698 intentional, suspected suicidal cannabis exposures were reported. Exposure counts increased by approximately 17% annually, most occurring in recent years among individuals between 14 and 64 years old. Nearly all cases involved more than one substance. Exposures in younger and older age groups occurred more frequently among females.

About 9.6% of exposures resulted in death or other major outcomes (life-threatening or with major residual disability or disfigurement). In older adults, 19.4% of exposures resulted in death or other major outcomes.

Reference: Graves JM, Dilley JA, Klein T, Liebelt E. Suspected suicidal cannabis exposures reported to US Poison Centers, 2009-2021. JAMA Netw Open. 2023;6(4). doi:10.1001/jamanetworkopen.2023.9044.

RENAL CELL CARCINOMA

Combination results in longer progression-free survival

Treatment with cabozantinib plus nivolumab and ipilimumab resulted in significantly longer progression-free survival than treatment with nivolumab and ipilimumab alone in patients with previously untreated, advanced renal-cell carcinoma who had intermediate or poor prognostic risk, according to a paper published in New England Journal of Medicine.

The authors conducted a phase 3, double-blind trial that included 855 patients with advanced clear-cell renal-cell carcinoma who had not previously received treatment and had intermediate or poor prognostic risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium categories. The patients were randomly assigned to receive 40 mg of cabozantinib daily in addition to nivolumab and ipilimumab (experimental group, 428) or matched placebo in addition to nivolumab and ipilimumab (control group, 427).

The primary endpoint was progression-free survival. The secondary endpoint was overall survival and assessed in all patients who had undergone randomization.

Of the first 550 patients who had undergone randomization (276 in the experimental group and 274 in the control group), the probability of progression-free survival at 12 months was 0.57 in the experimental group and 0.49 in the control group. About 43% of the patients in the experimental group and 36% in the control group had a response.

The authors write that Grade 3 or 4 adverse events occurred in 79% of the patients in the experimental group and 56% in the control group.

The authors note that follow-up for overall survival is ongoing.

Reference: Choueiri TK, Powles T, Albiges L, et al Cabozantinib plus nivolumab and ipilimumab in renal-cell carcinoma. N Engl J Med. 2023;388(19):1767-1778. doi:10.1056/nejmoa2212851.