Prior Authorization Requirements for Calcitonin Gene-Related Peptide Antagonists

ABSTRACT

Objectives: To determine whether broad categories of criteria exist among prior authorization (PA) policies from different managed care organizations (MCOs) and to identify similarities and differences among MCO coverage requirements for medications within the calcitonin gene-related peptide (CGRP) antagonist class.

Study Design: Quantitative and qualitative descriptive analysis.

Methods: PA policies from different MCOs for erenumab, fremanezumab, galcanezumab, and eptinezumab were identified through a comprehensive online search. Individual criteria from each policy were analyzed and grouped into both broad and specific categories. Descriptive statistics were used to identify and summarize trends among policies.

Results: A total of 47 MCOs were included in the analysis. The vast majority of policies applied to galcanezumab (n = 45; 96%), erenumab (n = 44; 94%), and fremanezumab (n = 40; 85%), with fewer policies for eptinezumab (n = 11; 23%). There were 5 broad categories of PA criteria found to be included in coverage policies: prescriber specialization (n = 21; 45%), prerequisite drugs (n = 45; 96%), safety considerations (n = 8; 17%), and response to therapy (n = 43; 91%). The final category, titled appropriate use, included any criteria meant to ensure appropriate medication use and included age requirements (n = 26; 55%), suitable diagnosis (n = 34; 72%), exclusion of other diagnoses (n = 17; 36%), and exclusion of concurrent medications (n = 22; 47%).

Conclusions: This study identified 5 broad categories of PA criteria used by MCOs in the management of CGRP antagonists. However, within these categories, specific criteria from different MCOs varied significantly.

Am J Manag Care. 2023;29(4):e117-e123. https://doi.org/10.37765/ajmc.2023.89352

Takeaway Points

Using calcitonin gene-related peptide antagonists as a case study, this qualitative analysis identified significant differences in prior authorization (PA) criteria across managed care organizations (MCOs), which may contribute to patient and provider confusion.

• There are 5 broad categories of PA criteria commonly included in coverage policies: prescriber specialization, appropriate use, prerequisite drugs, safety considerations, and response to therapy.
• Within these categories, the stringency of MCOs’ requirements differs significantly.
• Using these broad categories as a guide may help improve consistency among MCOs and help providers navigate PA requirements more effectively.

Calcitonin gene-related peptide (CGRP) antagonists have emerged as important therapeutic options for migraine treatment and prophylaxis. The market for CGRP antagonists is extremely large, as more than 1 billion individuals worldwide experience migraines each year.¹ However, use of these agents may be limited due to a high cost burden.¹ To date, 8 CGRP antagonists have been approved by the FDA, 6 of which have been approved for migraine prophylaxis: erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, and, most recently, atogepant.^2-7 The remaining CGRP antagonists, ubrogepant and zavegepant, are indicated only for migraine treatment and share this indication with rimegepant.^8,9

Prior authorization (PA) is a common tool used by managed care organizations (MCOs) to ensure appropriate and cost-effective medication utilization.¹⁰ The use of PA is common for high-cost medications, therapies that may be used inappropriately (eg, off-label indications), and for medication classes in which various clinically similar options exist. For all these reasons, many MCOs have instituted PA requirements on the CGRP antagonist class. However, PA criteria are not universal and are determined based on each MCO’s review of clinical evidence, financial resources and agreements, and/or population demographics.^10,11 Additionally, an MCO’s ability to develop new policies or update existing criteria may be hindered by factors outside its control, including regulatory restrictions, logistical challenges, and administrative limitations. Consequently, requirements may differ across MCOs, affecting patients and providers. Providers have described the PA process as a high burden, leading to delays in care, discarded treatment recommendations, and negative health outcomes for patients.¹²

PA policies for different medication classes have been explored in the literature, with a majority focusing on each state’s Medicaid policies for the selected drug class.^13-18 Additionally, recent data suggest stark differences in the application of prescriber requirements to coverage decisions.¹⁹ Overall, evidence suggests that wide differences in criteria among policies exist, resulting in discrepancies of clinical appropriateness and restricted access for patients. Despite these available data, research defining the broad types of PA criteria used by MCOs is scarce. To address this gap and summarize new information regarding a high-profile medication class, we examined trends in PA requirements for CGRP antagonists among MCOs.

METHODS

We conducted a qualitative and quantitative descriptive analysis of CGRP antagonist PA policies. Policies were identified through a comprehensive online search using Google in July 2020 using prespecified search terms (eAppendix Table 1) (eAppendix available at ajmc.com). As required by the institutional review board, upon locating publicly posted policies online, we attempted to contact each MCO to request permission on an opt-out basis to include the MCO’s policy in the analysis. The MCOs were informed that each organization would remain anonymous, results would be shared only in the aggregate, and no exact language from policies would be used.

All lines of business (LOBs) were included (ie, commercial, health care reform, Medicaid, Medicare), and policies for which the LOB could not be identified were categorized as “unspecified.” National, regional, and state MCOs were represented. In addition, all MCO types (eg, health plans, pharmacy benefit managers) were included.

To limit the scope of the study, only pharmacy benefit policies for erenumab, fremanezumab, galcanezumab, and eptinezumab for migraine prophylaxis were considered for analysis. Rimegepant and atogepant did not gain FDA approval for migraine prophylaxis until after the analysis was complete. All policies and requirements for ubrogepant, rimegepant, and zavegepant for migraine treatment; criteria for galcanezumab with regard to cluster headache prophylaxis; and medical policies for eptinezumab were excluded.

Policies effective from July 2019 to July 2020 were included to account for a 1-year look-back from the time of analysis. Policies were included only if an effective date could be located. Policies were excluded if a request was received by the MCO to not be included or if no contact information for any individual from the MCO could be found. The most recent version of any MCO’s policies was used if multiple versions were found.

The MCOs for which policies were located from multiple LOBs (eg, a commercial policy and a Medicare policy) or for multiple agents (eg, a commercial policy covering erenumab and a second commercial policy covering fremanezumab) were analyzed for differences among the identified criteria. If the simple majority (ie, greater than 50%) of criteria differed among policies, the MCO was excluded from the study. If fewer than half of the criteria differed, only the stricter of the available criteria were included and analyzed as 1 set of criteria for 1 MCO. See eAppendix Table 2 for examples of these instances and how they were analyzed.

We used descriptive statistics to identify and summarize trends among policies. Policies were first organized by the medication(s) included and the indications covered. From here, individual criteria from each policy were analyzed and grouped into both broad and specific categories. There were 5 broad categories of PA criteria developed: requirements on prescriber specialization, appropriate use, prerequisite drugs, safety considerations, and response to therapy. Although it is not a PA criterion itself, a sixth category of authorization length was also used. Quantity limits and any other limitations of coverage not explicitly stated in each policy’s criteria were not included in the analysis.

Several terms were defined during the analysis to ensure consistency (eAppendix Table 1). This project was determined to be exempt from review by the Wilkes University Institutional Review Board.

RESULTS

Policies from 47 MCOs were included in the analysis (Figure 1). The vast majority of policies applied to galcanezumab (n = 45; 96%), erenumab (n = 44; 94%), and fremanezumab (n = 40; 85%), with fewer policies for eptinezumab (n = 11; 23%). Additional MCO characteristics and full results can be found in Table 1 and eAppendix Table 3, respectively.

Prescriber Specialization

A prescriber requirement, indicating that the agent must be prescribed by or in consultation with a certain specialist, was included by 21 (45%) MCOs. Of these 21 MCOs, 20 (95%) required the prescription to be written by or in consultation with a specialist, whereas 1 (5%) accepted only prescriptions written by a specialist.

Of the 21 MCOs that required specialist involvement, 20 (95%) considered neurologists as appropriate specialists, with 1 (5%) MCO not stipulating the type of specialist required; 11 (52%) MCOs also accepted pain specialists, whereas 9 (43%) also accepted headache specialists (Figure 2).

Appropriate Use

Appropriate use was considered to be any criteria that ensured that the patient was a candidate for the medication based on FDA labeling and/or clinical evidence. The first component of appropriate use, an age requirement, was included by 26 (55%) MCOs. Of these, the age requirement was listed as 18 years or older by 24 (92%) MCOs, whereas 2 (8%) specified that the patient’s age had to be appropriate based on the requested medication’s labeling.

Appropriate use also involves a suitable diagnosis or indication, which was required by 34 (72%) MCOs. Of these, 7 (21%) MCOs accepted migraine with or without aura, whereas 24 (71%) accepted episodic or chronic migraine; 21 of the 24 (88%) MCOs accepting episodic or chronic migraine specified a certain number of migraine and/or headache days to define the type of migraine. The defined number of days varied among both diagnoses (eAppendix Table 1), but the most variation was seen in how MCOs defined episodic migraine. Of the 21 MCOs that defined episodic migraine, the most common definition of either “less than 15 headache days per month” or “4 to 14 migraine days per month” was included by only 8 (38%), with added inconsistency related to a required amount of time (eg, 3 months) since symptom onset.

Similarly, 17 (36%) of the 47 MCOs looked for prescribers to exclude diagnoses of medication overuse headache (n = 15; 88%); other headache disorders (n = 4; 24%), such as rebound headache, medication withdrawal headache, cluster headache, and hemiplegic migraine; and other medical conditions that contribute to migraine headache (n = 3; 18%), such as sleep disorders, jaw disorders, and cardiovascular disorders.

Finally, appropriate use involved ensuring that certain medications will not be used concurrently. This was included by 22 (47%) MCOs. In this analysis, the medications restricted from concomitant use with the requested CGRP antagonist were other agents within the same class (n = 19; 86%) or onabotulinumtoxinA (n = 18; 82%).

Prerequisite Drugs

Nearly all MCOs (n = 45; 96%) included criteria requiring a previous trial and failure of at least 1 non–CGRP antagonist medication for migraine prophylaxis, with the majority of these MCOs necessitating a previous trial of 1 (n = 13; 29%) or 2 (n = 25; 56%) alternative medications before the requested agent could be approved. The remaining 7 (16%) MCOs required a previous trial of 3 alternatives (Figure 2).

The MCOs differed with regard to the specificity of the agents tried in the past. Twenty-one (84%) of the 25 MCOs that required a previous trial of 2 alternatives required those alternatives to be from different drug classes, whereas the remaining 4 (16%) also accepted previous therapies from the same class. Similarly, 6 (86%) of the 7 MCOs that required 3 medications to be tried first required all 3 agents to come from different drug classes.

In addition, 28 (62%) of the 45 MCOs requiring a previous trial of a non–CGRP antagonist medication for migraine prophylaxis specified a required length of the trial, although no consensus among MCOs was identified. Of these, 7 (25%) MCOs required each medication to have been tried for a minimum of 4 weeks, 4 (14%) specified at least 6 weeks, 10 (36%) stated at least 8 weeks, and 7 (25%) noted at least 12 weeks.

Of the 45 MCOs that required alternative medications for migraine prophylaxis to be trialed, 44 (98%) listed the alternatives as either the names of individual medications (eg, propranolol) or the medications’ classes (eg, β-blockers), whereas 1 (2%) did not specify which agents were considered appropriate alternatives. Listing alternatives by class name was done by 37 (84%) of these MCOs, whereas 7 (16%) included medication names without listing classes. See Table 2 for more detail.

Of these 44 MCOs that listed alternatives, the most commonly accepted medications or classes included anticonvulsants (n = 44; 100%), β-blockers (n = 43; 98%), and antidepressants (n = 39; 89%). Less frequently mentioned were angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (n = 9; 20%), calcium channel blockers (n = 8; 18%), and onabotulinumtoxinA (n = 8; 18%). See Figure 3 for more detail.

Eighteen (40%) MCOs, all of which required prerequisite non–CGRP antagonist therapies, also required a previous trial of 1 (n = 8; 44%) or 2 (n = 10; 56%) preferred agents within the CGRP antagonist class before approval (Figure 2). The most commonly preferred agents were galcanezumab (n = 13; 72%) and erenumab (n = 13; 72%), followed by fremanezumab (n = 6; 33%), with none preferring eptinezumab.

Safety Considerations

Criteria built around safety considerations, such as confirming the absence of adverse events, contraindications, or pregnancy, were included by 8 (17%) MCOs. Of these 8 MCOs, 5 (63%) considered safety in both their initial and reauthorization criteria.

Duration of Authorization and Response to Therapy

There were 39 (83%) MCOs that specified an authorization duration in their policy for initial and reauthorized approvals (Figure 2). Of these 39 MCOs, 20 (51%) limited initial approval to 3 months, 14 (36%) listed a 6-month duration, and 5 (13%) allowed for a 12-month approval. Reauthorization time frames tended to be longer in duration, with 5 (13%) MCOs noting a 6-month duration, 33 (85%) citing a 12-month duration, and 1 (3%) having an open-ended reauthorization period.

Forty-three (91%) MCOs included reauthorization criteria, and all required a response to therapy to occur for the requested agent to be reauthorized. Most MCOs (n = 28; 65%) included more than 1 consideration of what constitutes a response to therapy. The most commonly accepted definitions were a reduction from baseline in the number of migraines (n = 38; 88%), in migraine severity (n = 19; 44%), and in the use of acute migraine abortive medications (n = 10; 23%).

DISCUSSION

When analyzing the PA criteria for CGRP antagonists, we identified significant inconsistencies among requirements, despite successfully defining 5 broad categories of PA criteria.

One area of inconsistency was a difference in prescriber specialty requirements among MCOs that included this criterion. Managed care organizations differ on whether specialists are required to prescribe CGRP antagonists, with more than half of MCOs not including this requirement. When a specialist was required, there was additional inconsistency regarding which specialist(s) are appropriate. However, each MCO’s awareness of specialist options within its network may account for some of the differences in prescriber requirements.

We also identified inconsistencies within the broad category of appropriate use, in which some MCOs included an age requirement as a specific age (ie, 18 years or older) as opposed to an appropriate age based on the medication’s labeling. If the medication covered by the policy were to receive an expanded age indication from the FDA, requiring a specific age can lead to a potentially inappropriate denial of care for the expanded population. However, many MCOs alleviate this concern by having mechanisms in place to allow for approval of expanded indications prior to formal policy modification.

According to their package inserts, all of the agents included in our study are FDA-approved for the preventive treatment of migraine in adults and were studied in patients with episodic migraine and chronic migraine.^2-5 Although the diagnosis requirement was included in most MCO policies, the definitions of the number of migraine or headache days required to confirm a diagnosis varied significantly, especially for episodic migraine. This difference appears to reflect an inconsistency of each medication’s pivotal clinical trial inclusion criteria.^2-5 Different diagnosis definitions among MCOs emphasize that PA criteria is determined by each MCO’s clinical review of available literature.¹⁰

One of the few consistent areas among MCOs was requiring prerequisite drugs. However, the chosen verbiage used by MCOs differed, and this creates ambiguity for patients, providers, and possibly even those reviewing the medication requests from within each MCO. Choosing to list only individual drug names or classes, using definitive or example language, and employing various numbers of classes and trial lengths increases the complexity of coverage requirements among MCOs. Based on their interpretation of existing evidence, guidelines, and clinical compendia, certain MCOs may consider more migraine prophylaxis medications “appropriate” compared with other MCOs, leading to additional patient choice.^20-22

Response to therapy as a reauthorization criterion was included by nearly all MCOs, but what was considered a positive response to therapy varied. Some MCOs were more particular with their requirements (eg, a decrease by a specific number of headache days), whereas some were more open ended and accepted any measure of improvement. The wide variety of reauthorization criteria identified through this analysis emphasizes differing opinions about appropriate disease control measures and their role in confirming medication efficacy. PA requirements, including reauthorization criteria, must strike a balance among provider autonomy, appropriate medication use, and cost containment.

Our study contributes to the existing literature on the topic of coverage differences among MCOs.^13-18 The number of PA policies analyzed in our study and the inclusion of all LOBs add to the current literature, reinforcing the idea that variation in PA criteria exists across multiple LOBs.¹⁷ Although PA is an effective cost-management tool and helps ensure appropriate medication utilization, our findings support previous conclusions that inconsistencies in PA requirements among MCOs can lead to an administrative burden for providers and delayed care for patients. Providers and patients should consider an MCO’s formulary and utilization management options when recommending treatment or choosing coverage, as a disruption in medication access can affect the patient’s condition.¹¹ Although consistency with clinical evidence is ideal, some degree of variation may be inevitable due to MCO-specific factors. Still, this variation may be desired, as it can create choice in benefit design for patients.

The intention of this study is not to identify or propose a “correct” set of PA requirements for CGRP antagonists. Instead, we aimed to identify similarities and differences among existing criteria to highlight trends and improve consistency among MCOs. Additionally, as providers desire a greater sense of transparency with regard to MCOs’ PA criteria, we looked to offer providers a broad sense of the types of criteria commonly used by plans. Armed with this knowledge, health care providers may more effectively navigate the PA process, despite not knowing an individual MCO’s specific criteria.

Limitations

Our study has several limitations. Although we were able to conduct a thorough analysis of each policy identified through our comprehensive online search, whether all relevant policies were found is undeterminable. Still, the qualitative analysis reached a point of data saturation well before the full data set was evaluated.²³

The structure of each MCO’s PA policy differed, with some including criteria, such as an appropriate indication or the exclusion of concomitant medications, under alternate sections (eg, “Covered Uses,” “Background,” “Limitations of Coverage”). Because it is unclear how these are used by MCOs, we chose to exclude these sections, which may have affected our analysis. For example, whereas 34 MCOs required an appropriate diagnosis as part of their criteria, the remaining 13 mentioned the diagnosis elsewhere in their policies. That said, these sections consistently contained similar requirements to other approval criteria, so the defined categories of criteria would have not been affected.

Our decision to incorporate only the more restrictive criteria when more than 1 policy was identified for a given MCO may introduce bias. Although it is possible that stricter criteria are more specific and would inherently lead to a greater degree of variation in our findings, this applied to a small number of MCOs and did not impact the overall findings in a meaningful way.

Finally, we did not report any criterion that was incorporated by an MCO if it could not be appropriately reworded to maintain anonymity. However, unreported unique criteria represented rare circumstances that would not have affected the overall findings. To further protect anonymity, we did not detail inconsistencies in criteria by different LOBs, MCO types, or geographical locations. Due to the random distribution of the identified policies within these categories, regulatory factors were unlikely to influence the overall findings.

CONCLUSIONS

This study identified 5 broad categories of PA criteria used by MCOs in the management of CGRP antagonists. However, within these categories, specific criteria from different MCOs varied significantly.

Acknowledgments

The authors wish to thank Luke Minnich for his contributions to the data collection and analysis for this project.

Author Affiliations: Nesbitt School of Pharmacy, Wilkes University (LM, SK), Wilkes-Barre, PA.

Source of Funding: None.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (LM, SK); acquisition of data (LM, SK); analysis and interpretation of data (LM, SK); drafting of the manuscript (LM, SK); critical revision of the manuscript for important intellectual content (LM, SK); statistical analysis (LM, SK); provision of patients or study materials (LM, SK); administrative, technical, or logistic support (LM, SK); and supervision (LM, SK).

Address Correspondence to: Lindsay Musial, PharmD, Nesbitt School of Pharmacy, Wilkes University, 84 W South St, SLC 336, Wilkes-Barre, PA 18702. Email: lindsay.musial@gmail.com.

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