Two just lately accomplished analyses of extremely purified cannabidiol (CBD) used to cut back seizures in Lennox Gastaut syndrome (LGS) have proven the formulation as an add-on remedy is efficient in decreasing seizures out to three years however that it could additionally trigger thrombocytopenia in kids on concurrent valproic acid remedy.
On the 2020 CNS-ICNA Conjoint Assembly, held nearly this 12 months, Anul Patel, MD, part chief of Pediatric neurology at Nationwide Kids’s and affiliate professor of scientific pediatrics and neurology on the Ohio State College, each in Columbus, Ohio, reported 156-week outcomes of an open-label extension trial referred to as GWPCARE5 that confirmed sufferers with LGS taking Epidiolex had a 60% or larger common discount in seizures, in contrast with baseline. Epidiolex, a extremely purified type of CBD, was accepted by the Meals and Drug Administration in 2018 for LGS and Dravet syndrome.
In a separate presentation, Nancy A. McNamara, MD, an assistant professor on the C.S. Mott Kids’s Hospital on the College of Michigan, Ann Arbor, mentioned that greater than one-third of sufferers taking each Epidiolex and valproic acid (VPA) developed thrombocytopenia after beginning CBD remedy. The only-center chart evaluate she reported on included 83 sufferers.
Daniel Friedman, MD, an epilepsy specialist at New York College who’s researched CBD in kids with autism spectrum disorder, mentioned, “These research present that, whereas purified CBD has sturdy results on essentially the most disabling seizures in kids and adults with LGS, like all remedies, it’s not with out dangers that warrant consideration and monitoring.”
Open-Label Extension Research
The open-label extension examine included 366 sufferers who participated within the two earlier scientific trials. They got various doses of CBD titrated over 2 weeks with 20 mg/kg because the goal dose, Patel mentioned. The most typical concurrent therapies they had been taking had been clobazam, valproate or VPA, lamotrigine, levetiracetam, and rufinamide. At weeks 145-156, 67% of sufferers had a 50% or larger discount in seizures, 44% had a 75% or larger discount, and 9% stopped having seizures altogether, Patel mentioned.
“CBD remedy had an analogous security profile to what was noticed within the accomplished mother or father randomized scientific trials,” Patel mentioned. “Sustained reductions in drop and complete seizures had been noticed as much as the 156-week follow-up level. So these outcomes display the potential long-term advantages of CBD remedy for sufferers with LGS because it pertains to discount of their seizures.”
Antagonistic occasion profiles on this evaluation had been much like earlier scientific trials, he famous. The three most typical opposed occasions had been diarrhea (38%), convulsion (38%) and pyrexia (34%), however excessive percentages of these opposed occasions resolved throughout follow-up: 78%, 80%, and 96%, respectively.
Patel additionally famous that 31% of sufferers had elevated liver enzymes (alanine aminotransferase or aspartate aminotransferase), however most of those sufferers – 78 of 113, or 69% – had been on concomitant VPA. “Importantly, no affected person met the usual standards for extreme drug-induced liver harm, referred to as Hy’s legislation,” he mentioned.
Retention charges for sufferers had been 81% at 1 12 months, 69% at 2 years and 65% at 3 years, Patel mentioned.
“An Pressing Systemic Evaluation”
McNamara’s analysis drilled down into the interplay of CBD and VPA. “Over the previous a number of months we have now made observations that a number of sufferers that had been began on CBD, also referred to as Epidiolex, had developed thrombocytopenia, a few of which had been symptomatic,” she mentioned. Signs included hematuria, straightforward bruising, and gingival bleeding.
That prompted what McNamara referred to as “an pressing systemic evaluate” of all sufferers on CBD. Of 83 sufferers began on CBD for LGS from January to August 2019, 9 (11%) developed thrombocytopenia. “All of those sufferers had been on concurrent VPA and no sufferers began on CBD with out VPA developed thrombocytopenia,” she mentioned. In all, 23 sufferers had been taking CBD concurrently with VPA. 4 of 9 instances had been symptomatic.
“The thrombocytopenia was reversible in all sufferers with discount of remedy and one affected person recovered spontaneously with out intervention,” McNamara famous.
“This was an vital discovering as a result of this was not one thing that had come out of the scientific trials previous to FDA approval,” McNamara mentioned. “This requires nearer monitoring for sufferers who’re began on CBD who’re already on VPA.”
Of the 23 sufferers taking concurrent VPA, 10 had low platelet counts after beginning CBD. In six sufferers, platelet counts dropped from regular earlier than CBD remedy to low afterward.
The examine used a McNemar take a look at to find out if an noticed opposed occasion occurred by likelihood or was associated to beginning a drug, which yielded a P worth of .125, McNamara mentioned. “Whereas this didn’t obtain statistical significance, we recommend that prescribers intently monitor platelet ranges after beginning CBD, notably when a affected person can also be on concurrent VPA,” she mentioned.
Her group obtained a whole blood rely at baseline after which at 1, 3, and 6 months after beginning the affected person on CBD, together with analysis of alanine aminotransferase and aspartate aminotransferase. “We imagine that that is useful as a result of a lot of the sufferers that develop low platelets did so inside 3 months of beginning cannabidiol,” McNamara mentioned.
She acknowledged the boundaries of the single-center examine. “Future analysis will should be finished with bigger cohorts with standardized surveillance labs,” she mentioned in an interview.
Patel disclosed monetary relationships with GW Analysis and Greenwich Biosciences. McNamara has no related disclosures.
This text initially appeared on MDedge.com, a part of the Medscape Skilled Community.