Multiple Sclerosis Medications in the VHA: Delivering Specialty, High-Cost, Pharmacy Care in a National System
Introduction/Importance: Pharmacotherapy for multiple sclerosis has increased significantly since 1993 when the first disease modifying therapy was approved. The expansion of therapies has been accompanied with differences in adverse effect profiles, efficacy, and cost. The most recent therapies pose the challenge of balancing these issues while providing optimal care.
Observations: Several measures such as generic conversion and standardization of therapies can be employed to control costs of therapy. The safety and efficacy of these agents can be monitored by implementation of criteria for use and/or medication utilization evaluations.
Conclusions: A formulary management system encompasses methodologies to evaluate the relevant clinical and medical literature and includes a systematic approach for selecting medications for different diseases, conditions, and patients. Formulary systems often contain prescribing guidelines and clinical recommendations that assist health care professionals with providing high quality, value-based care for patients.
The overall outpatient pharmacy costs for veterans have remained constant despite the reduction in outpatient pharmacy prescription numbers. This may be due to increases in DMT cost to the VHA and the use of more expensive oral agents over the previously used platform injection DMTs.
Generic Conversion
GA is available in 20 mg daily and 40 mg3 times weekly subcutaneous injection dosing. The first evidence of clinical efficacy for a generic formulation for GA was evaluated by the GATE trial.7 This trial was a multicenter, randomized, double-blind, active- and placebo-controlled phase 3 trial. Eligible participants were randomized to receive daily SC injection for 9 months of 20 mg generic GA (n = 5,353), 20 mg brand GA (n = 5,357), or placebo (n = 584). The primary endpoint was the mean number of gadolinium (Gd1) lesions visible on MRIs during months 7, 8, and 9, which were significantly reduced in the combined GA-treated group and in each GA group individually when compared with the placebo group, confirming the study sensitivity (ie, GA was effective under the conditions of the study). Tolerability (including injection site reactions) and safety (incidence, spectrum, and severity of adverse events [AEs]) were similar in the generic and brand GA groups. These results demonstrated that generic and brand GA had equivalent efficacy, tolerability, and safety over a 9-month period.7
Results of a 15-month extension of the study were presented in 2015 and showed similar efficacy, safety, and tolerability in participants treated with generic GA for 2 years and patients switched from brand to generic GA.8 Multiple shifts for GA occurred, most notably the conversion from branded Copaxone (Teva Pharmaceutical Industries) to generic Glatopa (Sandoz). Subsequently, Sandoz released a generic 40 mg 3 times weekly formulation. Additionally, Mylan entered the generic GA market. With 3 competing manufacturers, internal data from the VHA indicated that it was able to negotiate a single source contract for this medication that provided a savings of $32,088,904.69 between September 2016 and May 2019.
The impact of generic conversions is just being realized. Soon, patents will begin to expire for oral DMTs, leading to an expected growth of generic alternatives. Already the FDA has approved 4 generic alternatives for teriflunomide, 3 for fingolimod (with 13 tentative approvals), and 15 generic alternatives for dimethyl fumarate (DMF). Implementation of therapeutic interchanges will be pursued by VHA as clinically supported by evidence.
Criteria for Use
PBM supports utilizing criteria to help guide providers on DMT options and promote safe, effective, and value-based selection of a DMT. The PBM creates monographs and criteria for use (CFU) for new medications. The monograph contains a literature evaluation of all studies available to date that concern both safety and efficacy of the new medication. Therapeutic alternatives also are presented and assessed for key elements that may determine the most safe and effective use. Additional safety areas for the new medications such as look-alike, sound-alike potential, special populations use (ie, those who are pregnant, the elderly, and those with liver or renal dysfunction), and drug-drug interactions are presented. Lastly, and possibly most importantly in an ever-growing growing world of DMTs, the monograph describes a reasonable place in therapy for the new DMT.
