Cost-effectiveness of adrenocorticotropic hormone versus oral steroids for infantile spasms.

OBJECTIVE: To compare the effectiveness and cost-effectiveness of adrenocorticotropic hormone (ACTH) and oral steroids as first-line treatment for infantile spasm resolution, we performed a systematic review, meta-analysis, and cost-effectiveness study. METHODS: A decision analysis model was populated with effectiveness data from a systematic review and meta-analysis of existing literature and cost data from publicly available prices. Effectiveness was defined as the probability of clinical spasm resolution 14 days after treatment initiation. RESULTS: We included 21 studies with a total of 968 patients. The effectiveness of ACTH was not statistically significantly different from that of oral steroids (.70, 95% confidence interval [CI] = .60-.79 vs. .63, 95% CI = .56-.70; p = .28). Considering only the three available randomized trials with a total of 185 patients, the odds ratio of spasm resolution at 14 days with ACTH compared to high-dose prednisolone (4-8 mg/kg/day) was .92 (95% CI = .34-2.52, p = .87). Adjusting for potential publication bias, estimates became even more favorable to high-dose prednisolone. Using US prices, the more cost-effective treatment was high-dose prednisolone, with an incremental cost-effectiveness ratio (ICER) of $333 per case of spasms resolved, followed by ACTH, with an ICER of $1 432 200 per case of spasms resolved. These results were robust to multiple sensitivity analyses and different assumptions. Prednisolone at 4-8 mg/kg/day was more cost-effective than ACTH under a wide range of assumptions. SIGNIFICANCE: For infantile spasm resolution 2 weeks after treatment initiation, current evidence does not support the preeminence of ACTH in terms of effectiveness and, especially, cost-effectiveness.

Do Patients Require Inpatient Admission to Receive Adrenocorticotropic Hormone (ACTH)? A Survey of US-Based Prescribers.

We aimed to determine variation in treatment of newly diagnosed infantile spasms, focusing on details of adrenocorticotropic hormone (ACTH) administration using a Redcap questionnaire sent to members of the Child Neurology Society. Two hundred fifty-seven members responded. Eighty-four percent prescribers used ACTH to treat infantile spasms. Seventy-six percent always admit patients. There is no difference between prescriber type (epileptologist or other) and prescriber location (state-funded or non-state-funded hospital) for decision to admit. Electroencephalographic (EEG) confirmation of spasms and education for injection were the commonest reasons to admit. Only 45% of prescribers accurately estimated the cost of ACTH. Participants in the hospital vial program were significantly more likely to always admit patients for ACTH than those who did not participate in such a program (P = .02). Although having the hospital sample vial allows time to complete investigation of infantile spasms and eliminates delays in initiating ACTH, it adds significantly to the cost of therapy.

Health Care Rationing in a Just Society: The Clinical Effectiveness Model.

Representing 18% of gross domestic product, and projected to increase to 20% by 2022, health care costs in the United States are an unsustainable expense. The clinical effectiveness model of cost containment is an ethical and self-sustaining paradigm that can assist bending the health care-cost curve. As envisioned by Buyx et al, clinically effective care is aimed at making the practice of medicine more explicitly evidence based with the goals of improving clinical success, efficiency, and value. I provide a vision for applying the clinical effectiveness model to the American health care system. I illustrate its use with 2 examples from the practice of child neurology: DOC-band (helmet therapy) for the treatment of positional plagiocephaly-relatively inexpensive but ineffective, and adrenocorticotropic hormone for the treatment of infantile spasms-expensive but effective.

Cost-effectiveness analysis of antiepileptic drugs in the treatment of Lennox-Gastaut syndrome.

An economic model evaluated the costs and outcomes of adjunctive clobazam therapy for Lennox-Gastaut syndrome (LGS) compared with adjunctive lamotrigine, rufinamide, and topiramate. Clinical data were used to estimate baseline frequency and the percentage of drop-seizure reductions over 3 months (all comparators) and 2 years (rufinamide). Claims data from a large US health care plan were employed to estimate costs. After 3 months, 21.5% of those receiving clobazam were drop-seizure-free. Over a 3-month horizon, clobazam was more effective and less expensive than comparators, with the assumption that >0.77% of drop seizures required medical care. Below this threshold, topiramate was less costly than clobazam. With the base-case assumption that 2.3% of drop seizures were medically attended, costs for patients receiving clobazam totaled $30,147 versus $34,223-$35,378 for comparators. Clobazam was more efficacious and less costly than rufinamide over a 2-year horizon. The percentage of medically attended drop seizures was a driver of results. Clobazam treatment may be cost-saving.

Rufinamide: a pharmacoeconomic profile of its use as adjunctive therapy in Lennox-Gastaut syndrome.

Rufinamide (Inovelon®), a triazole derivative, is an oral antiepileptic drug approved in the EU as adjunctive therapy in the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥4 years. The efficacy of oral rufinamide as adjunctive therapy in patients with LGS uncontrolled on one to three concomitant antiepileptic drugs was demonstrated in a pivotal, 12-week, randomized, double-blind trial. Rufinamide significantly reduced the 28-day frequency of both drop attacks and total seizures compared with placebo, and significantly increased the proportions of patients experiencing a ≥50% reduction in each seizure frequency. A significantly higher proportion of rufinamide than placebo recipients recorded an improvement in seizure severity at the end of treatment. Reductions in the frequency of drop attacks and total seizures were maintained in a long-term (up to 3 years), open-label extension study. Oral rufinamide was generally well tolerated in patients with LGS. Somnolence and vomiting were the most common adverse events occurring more frequently with rufinamide than with placebo. Two pharmacoeconomic analyses, using decision-analysis models with 3-month cycles over a time horizon of 3 years, assessed the cost effectiveness and cost utility, respectively, of rufinamide compared with topiramate and lamotrigine as adjunctive therapy in patients with LGS from the perspective of the UK NHS. The cost-effectiveness analysis suggested that rufinamide would be associated with incremental costs of £62 (drop attacks) or £2151 (total seizures) per 1% increase in the number of patients achieving a >50% reduction in seizure frequency over 3 years. The cost-utility analysis predicted that the incremental cost per QALY gained for rufinamide compared with the next less-costly and undominated therapy would be more than 5-fold higher than the commonly accepted willingness-to-pay threshold range in the UK. In conclusion, the available pharmacoeconomic data indicate that rufinamide is more effective, but more expensive, than alternative adjunctive therapies approved for use in patients with LGS in the UK. Rufinamide would appear to be a cost-effective alternative to topiramate. Although rufinamide exceeds conventional cost-effectiveness thresholds when compared with lamotrigine, it may still be considered a valuable treatment option for a devastating orphan disease such as LGS.

Effect of price increase of adrenocorticotropic hormone on treatment practices of infantile spasms.

Intramuscular adrenocorticotropic hormone putatively constitutes the most efficacious treatment for infantile spasms. Adrenocorticotropic hormone in the United States is an "orphan drug," made by a single manufacturer. The price of adrenocorticotropic hormone increased almost 14-fold on August 27, 2007. We sought to evaluate the impact of this price increase on treatment practices at our institution, using a retrospective chart review of all children with infantile spasms treated during 2007-2009. We identified 97 patients whose spasms were treated using antiepileptic drugs, and we determined the length of stay for those hospitalized to initiate adrenocorticotropic hormone. Patients before the price increase were more likely to have been treated with adrenocorticotropic hormone as first medication, and were hospitalized 2.2 +/- 0.5 S.D. days for initiation. Patients after the price increase were more likely to have been treated initially with oral antiepileptic drugs rather than adrenocorticotropic hormone (P < 0.002). Those commencing adrenocorticotropic hormone after the price increase were hospitalized significantly longer (5.1 +/- 0.6 days S.D., P < 0.001). Treatment choices need to be evidence-based, but other factors often influence them.

Outcomes in treatment of infantile spasms with pulse methylprednisolone.

The authors report their experience with intravenous methylprednisolone for the treatment of infantile spasms. A pulse dose of 20 mg/kg intravenous methylprednisolone on each of 3 successive days, followed by a 2-month oral prednisolone taper, led to the rapid remission (range, 2-6 days) of infantile spasms in 5 of 10 (50%) infants. In the subgroup of infants treated within 1 month of onset, 5 of 6 (83%) experienced remission within 6 days. The authors estimate the medication cost of intravenous methylprednisolone with prednisolone taper to be less than $200. In comparison, the cost of a typical course of adrenocorticotropic hormone in the United States can exceed $70,000. Initial treatment with intravenous methylprednisolone and/or oral corticosteroids is a reasonable cost-effective approach to infantile spasms. The lack of serious side effects, low cost, availability, ease of administration, and comparable efficacy suggests that intravenous methylprednisolone merits consideration for study in randomized prospective trials.