The Logistics of Biologics

Numbers from the National Psoriasis Foundation (NPF) underline a clear reality that we as clinicians must all recognize: Psoriasis is undertreated in the United States. Given the number of advancements made in the realm of treatment in recent years, there doesn’t appear to be a good reason why so many psoriasis patients are not receiving adequate treatment. The arrival of biologic agents on the market seemed to satisfy the need for highly efficacious and relatively safe treatments for moderate to severe psoriasis. But for various reasons, access to biologics has been limited for patients, as only a certain percentage of dermatologists prescribe them. These agents have been on the market for several years and tested sufficiently, and yet for reasons ranging from clinical concerns to potentially cumbersome encounters with insurance companies and specialty pharmacies, they haven’t taken off as expected.

In this article I will explore some of these reasons and offer clinical and logistical tips for determining ideal candidates for biologic therapy, selecting the right treatment, and securing approvals.

Determining the Ideal Candidate and Selecting an Agent

The decision to prescribe a biologic stretches beyond clinical considerations and encompasses things such as insurance coverage and specialty pharmacies. I will address some of the details regarding the prescription/approval process later, but first it’s worth examining the clinical and practical aspects that will guide judgment in determining candidates for biologic therapy and selecting an agent.

While these decisions are best made on a patient-bypatient basis, a set of broad principles is useful to get started. Often I find that patients with moderate to severe psoriasis that haven’t responded to phototherapy are good candidates for biologic therapy. This is especially true for such patients who may be hesitant to use other systemic therapies, such a methotrexate, cyclosporine, or acitretin. Clinicians must also weigh other factors related to the patient’s personal circumstances. For example, biologics may be appropriate for patients who can’t get to the office often enough for phototherapy. Biologics may also be worth considering for the roughly 30 percent of psoriasis patients who also have psoriatic arthritis, since tumor necrosis factor (TNF) inhibitors have been shown to particularly benefit psoriatic arthritis.

In terms of differentiating between the biologics, let’s begin with mechanisms of action (MOA). For the TNF inhibitors, the difference in MOA is not especially significant. Both bind to TNF, but whereas adalimumab (Humira, AbbVie) is a monoclonal antibody, etanercept (Enbrel, Amgen/Pfizer) is a receptor protein. The only difference in this sense is that etanercept develops fewer antibodies than adalimumab. Studies have indicated that adalimumab has higher efficacy, with 71 percent of patients achieving PASI 75 with adalimumab, as compared to 49 percent with etanercept.

Certain patient factors may play into the decision, as well. For example, patients over 220 lbs. may fare better with adalimumab. The reason for this is that etanercept may lose some of its efficacy in heavier patients when they eventually step down from two shots per week to one shot per week. Etanercept also has a shorter half-life than adalimumab, which makes it a potentially more flexible option for patients who plan on becoming pregnant or have undergone surgery.

Although ustekinumab (Stelara, Janssen) is newer to the market, the data thus far have indicated that its efficacy is roughly similar to that of adalimumab. Regarding psoriatic arthritis, however, the data are not substantive enough to recommend ustekinumab in these patients. And while there were early concerns with ustekinumab about class-related major adverse cardiovascular events (MACE), new five-year data has relieved some of these worries.

Once you’ve weighed the safety and efficacy components of each biologic agent against an individual patient profile, the decision will ultimately come down to patient comfort. Some patients are more worried about risk, so therefore a TNF inhibitor might be more appropriate, since the TNF agents have been on the market for a longer period of time (four and a half million patient years) and there have been no safety blips on the radar screen since their approval. Thus, for safety-focused patients, etanercept may be the best choice, whereas those in the middle who want more clearance might opt for adalimumab. Also, patients who do not have psoriatic arthritis might want to try ustekinumab, which from the standpoint of convenience is the most efficient agent. The reason for this is that ustekinumab requires only one shot every three months, as compared to two shots every 12 weeks for the first 12 weeks and then one shot a week thereafter with etanercept, and one shot every week with adalimumab. Ustekinumab is also administered under medical supervision, so if compliance has been an issue with a particular patient in the past, or if the patient is coming to your office from a distance, it might be the ideal choice.

In terms of adverse events, in general the safety profiles of the biologics are fairly consistent. The broader risk for all biologics is that there is a less than one percent chance that the patient will end up in a hospital receiving intravenous (IV) antibiotic therapy for infection.

Insurance and Approval

Aside from clinical considerations, there is a whole other side of biologics that can be taxing on clinicians, staff, and of course, patients. Completing all the necessary legwork regarding approval and insurance reimbursement is an intricate and time-consuming process, which has possibly influenced some clinicians to avoid prescribing biologics for psoriasis. There can be no illusion that treating psoriasis often requires going to additional steps to ensure that patients are receiving the best treatments.

There is no simple or easy way to manage biologic approvals. Nevertheless, there are several ways that clinicians can expedite the process. One needs to be committed in order to do it effectively. In most cases, the work to secure an approval requires a staff member of your practice dedicated to handling paperwork and interacting with the pharmacy. There are many steps involved in getting a biologic agent approved (see the “Biologic Help Sheet” on the previous page), but not more than a midlevel provider can handle. There is a learning curve at the beginning, but once you have a system in place the process is not a major burden. Keep in mind that if you prescribe biologics with some regularity and do not have someone on staff to handle the logistics, those responsibilities will fall on clinicians and take away from seeing other patients. Having a designated assistant for these issues can be both time- and cost-effective.

Aside from appointing a practice staff member to handle logistical details of biologic approval, there are other tools that may aid in the approval process. For example, pharmaceutical companies are often very willing to educate you on how to successfully manage and maintain relationships with specialty pharmacies that are important for securing approvals. Most of us have representatives from the manufacturers of biologic agents (Amgen, Pfizer, AbbVie, Janssen, etc.), many of whom are able to offer insight into how to get a drug approved appropriately and can answer questions about which pharmacy to use, where to fax forms, and so on.

Every insurance company is different when it comes to requirements for the approval of biologic medications. For example, some require patients to have tried a systemic agent. There may also be restrictions on which pharmacies you may use to fill the prescription. You will likely also face scenarios in which a patient’s insurance does not cover biologic agents. If that’s the case, you should contact the company to see if they have a program for patients who can’t afford to get the drug and emphasize the importance of that particular agent for the patient’s health. Having a template letter for these needs may be useful for these purposes.

For more information on this and other administrative issues regarding biologics, visit the Nation al Psoriasis Foundation (www.psoriasis.org). And for more on the specific details of the approval process and resources to aid you along the way, see the “Biologic Help Sheet” (page 37).

Going the Extra Mile

When it comes to treating psoriasis, it is important that we fight for the drug that we feel will most benefit our patients. Those who don’t wish to take on the added burden of treating the full scope of psoriasis should refer to dermatologists that are willing to offer the appropriate treatment.

As more data are published and more patients are treated with these agents, it’s becoming clearer that biologics are an essential component in psoriasis care for patients with moderate to severe disease. As we come to learn more about these agents, we will become more proficient with marrying the right agent with the right patient. It may not always be easy to secure an approval, but remember that there are many resources and ways to help streamline the process. In a perfect world, we wouldn’t have to jump through so many hoops, but no matter what the challenges, the onus is on us to meet the needs of our patients.

Dr. Bagel has served as consultant, researcher, or speaker for Amgen, LEO, Abbott, Janssen, Galderma, and GlaxoSmithKline.

Jerry Bagel, MD, FAAD, is director of the Psoriasis Treatment Center of Central New Jersey.