Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Crohn's Disease.
Treatment: Humira (CF) 40mg / 0.4ml Injector Increase, Pre-service.
The insurer denied the Humira (CF) 40mg / 0.4ml Injector Increase, Pre-service.
The denial is upheld.

The patient is a male.

Pertinent to this review, the patient was diagnosed several years ago with entero-colonic Crohn's disease for which he had been, until recently, maintained on Humira 20mg (milligrams) weekly.  At his last colonoscopy, histology showed "mild chronic ileitis with rare granulomas, chronic colitis with mild activity, and rectosigmoidiitis with moderate activity."

At issue, the patient's provider advised immediate Humira dose escalation to 40mg (milligrams) subcutaneous weekly in response to a reportedly non-ideal serum drug level (not provided).  Per appeal letter, the patient has failed dose-escalated Remicade, pulse corticosteroids, and experienced break-through symptoms when Humira was dosed every two weeks.

The patient's health plan policy governing Humira use for children 17-<40 kg (kilograms) in weight does not cover the drug at doses greater than 20mg (milligrams) every other week.  The patient has since earlier in the year, been receiving twice the FDA (United States Food and Drug Administration)-approved adult dose regimen.  No re-evaluation of the patient was provided to support that 40mg (milligrams) weekly has been effective and safe, nor were provided rechecked therapeutic drug monitoring results to assess if drug serum levels increased.

No, the health plan should not cover the Humira (CF) 40mg / 0.4ml (milliliter)Injector Increase.

The patient has since earlier in the year, received twice the FDA (United States Food and Drug Administration)-approved adult dose regimen, predicated in part on one week of subjective symptoms and a sub-optimal serum drug level (not specified).  No re-evaluation of the patient was provided to support that increasing the patient's Humira from 20mg (milligrams) weekly to 40mg (milligrams) weekly has been effective and safe, nor were provided rechecked therapeutic drug monitoring results to assess if drug serum levels increased.

The medical appropriateness for the dose escalation under review is uncertain. At the time of dose increase to 40mg (milligrams) weekly, the patient's inflammatory markers were little changed from his previous baseline, he was not anemic, was not manifesting leukocytosis, his albumin level had improved and a substantial weight gain was documented. No objective exam findings nor imaging results were provided, and no stool study results were included to exclude that infection rather than a Crohn's flare accounted for his symptoms as reported.

No, the Humira (CF) 40mg / 0.4ml Injector Increase is not likely to be more beneficial.

Humira (adalimumab) is indicated for the treatment of moderately to severely active Crohn's disease in adults and pediatric patients six years of age and older. (1) Adalimumab is administered by subcutaneous injection every two weeks. For adults and children 40 kg (kilograms) body weight, the manufacturer's label recommends a loading dose of 160 mg (milligrams), followed by 80 mg (milligrams) two weeks later, and 40 mg (milligrams) every two weeks for maintenance. For children 17 to 40 kg (kilograms) body weight, the loading dose is 80 mg (milligrams), followed by 40 mg (milligrams) two weeks later, and 20 mg (milligrams) every two weeks for maintenance. Escalation to weekly dosing is often necessary, guided by the clinical response.

However, in the absence of objective data to the contrary, the patient's disease may not be of a severity to meet FDA (United States Food and Drug Administration) labeling for Humira. Certainly his current 40mg (milligrams) weekly dose is off-label. Of concern, the risk of the patient's present Humira dosing may exceed benefit. Indeed, available records do not afford a glimpse at the efficacy and safety of the drug in the patient's case since no re-evaluation was provided.

The medical appropriateness for the patient's dose escalation under review is uncertain. At the time of dose increase to 40mg (milligrams) weekly, the patient's inflammatory markers were little changed from his previous baseline, he was not anemic, was not manifesting leukocytosis, his albumin level had improved and a substantial weight gain was documented. No objective exam findings nor imaging results were provided, and no stool study results were included to exclude that infection rather than a Crohn's flare accounted for his symptoms as reported.

Further, the manufacturer's web site (1) notes that Humira carries substantial pediatric risk. Lymphoma and other malignancies have been reported in children, including hepatosplenic T-cell lymphoma which may have a very aggressive disease course and be fatal.