Use of Retail Pharmacies Linked to Higher Nonadherence in RA


A recent exploratory study found signs that retail pharmacies may be associated with higher nonadherence to rheumatoid arthritis (RA) medications.

A recent exploratory study found signs that retail pharmacies may be associated with increased nonadherence to rheumatoid arthritis (RA) medications.

In addition, methotrexate use alone was not associated with lower healthcare costs, excluding specialty RA agents, the study reported. But adherence to methotrexate and etanercept was associated with lower healthcare costs, excluding specialty RA agents, versus non-methotrexate users.

Methotrexate use may also be associated with increased persistence, the researchers said.

The study sought to examine differences in adherence, persistence, switch patterns, and healthcare costs among high-cost, specialty anti-inflammatory medications, and suggest risk factors for nonadherence in RA. In addition, adherence, persistence, and costs of care were also examined for concurrent methotrexate use for the most-used targeted drugs.

In this retrospective study, researchers used medical and pharmacy claims from 1.2 million enrollees in commercial health plans administrated by Premera Blue Cross, the largest not-for-profit health plan in the Pacific Northwest.

Anti-inflammatory and disease-modifying antirheumatic drugs are the staples of RA therapies. Conventional synthetic disease modifying agents, such as methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine, are commonly used as first-line treatments.

Patients who fail first-line therapy or have severe initial disease require more costly specialty biologic agents, such as abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, sekukinumab, tocilizumab, ustekinumab, and rituximab, or a newer small-molecule treatment, tofacitinib.

However, inflammatory conditions are one of the most expensive classes for drug spending, with an average prescription costing $3587.83. Adherence is often poor (about 40% but as high as 75%); low adherence results in poor outcomes and increased costs.

There is a lack of real-world evidence for newer agents, such as tofacitinib (an oral drug that inhibits Janus protein kinases), golimumab, and certolizumab, a soluble tumor necrosis factor (TNF) receptor or Fab fragments against TNF.

In this study, patients were included if they used abatacept, adalimumab, anakinra, apremilast, certolizumab, etanercept, golimumab, infliximab, rituximab, sekukinumab, tocilizumab, tofacitinib, and ustekinumab.

Adherence was calculated via medication possession ratio. Persistence was calculated as the amount of days between the initial fill and final fill plus days supply.

Switch rates for adalimumab and etanercept were calculated as the percentage of members who switched to another target drug during the observation period. Direct medical costs (total healthcare costs) and healthcare costs excluding specialty agents were calculated using the net allowable amount per claim for the duration of each therapy.

Included in the analysis were 456 members (101 male and 355 female) and 6943 claims; most claims were filled by females and were filed by patients aged 45-65 years.

Relative to specialty pharmacies, retail was associated with 9% higher nonadherence.

The most used drugs by patient and claim count were etanercept (38% of claims), followed by adalimumab (35%) and abatacept (5%).

The most commonly switched-to drug after adalimumab/etanercept was abatacept (n = 39). The mean time to switch to any drug was 244 days from adalimumab and 292 days from etanercept. Median time to switch from etanercept to adalimumab was 358 days (n = 25) and from adalimumab to etanercept was 336 days (n = 18). Overall switch rates for adalimumab and etanercept were 35% and 34%, respectively. In addition, index switch rates for adalimumab and etanercept were 25% and 26%.

Nonadherence in certain subgroups was associated with higher mean monthly healthcare costs, excluding specialty agents (etanercept cohort: +$1,063 for nonmethotrexate users; +$492 for nonadherent methotrexate users), but adherence was associated with higher total healthcare costs (+$883 for etanercept).

Relative to specialty pharmacies, retail was associated with 9% higher nonadherence.

Concurrent methotrexate use was associated with higher persistence (+307 and +192 days with adalimumab and etanercept, respectively).

The authors noted that Premera’s medical policy prefers adalimumab and etanercept as preferred formulary agents. The findings about indicate a possible risk factor for nonadherence stemming from retail pharmacy use, they wrote.

They also emphasized that the study showed an association between improved adherence and increased total healthcare costs. However, they said it is possible that additional biologic/biosimilar approvals may impact high drug prices, easing any financial burden from improved adherence.


Khilfeh I, Guyette E, Watkins J, Danielson D, Gross D, Yeung K. Adherence, persistence, and expenditures for high-cost anti-inflammatory drugs in rheumatoid arthritis: an exploratory study. J Manag Care Spec Pharm. 2019;25(4):461-467. doi: 10.18553/jmcp.2019.25.4.461.

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