Each weeknight between 6:58 and 7:00 pm EST, somewhere between the end of the ABC World News and Jeopardy!, two to three commercials for biologic agents typically air. They begin by showing how an improved quality of life can be obtained through treatment, but they end with the ominous warning that you might get tuberculosis, lymphoma, or die. In an attempt to improve their psoriasis, many patients will go ahead and make an appointment with the dermatologist but have anxiety about the risk profile of the treatment options that are available. And while it is the duty of pharmaceutical companies to report worst-case scenarios, these warnings sometimes paint a more negative picture of these therapies in the minds of patients.
In reality, treatment with biologic agents is not a simple process. Not only are the agents themselves often times difficult to access; patients must be screened thoroughly for a host of potential adverse events even if they have a clear path to access. However, for qualified candidates without any contraindications, clinical trial data and fiveyear post-marketing data indicate about a one percent increase in serious infections, and possibly a one in 5,000- 10,000 of lymphoma associated with biologic treatment. In real life terms, it is about the same risk of getting into a severe car accident while driving to the office.
Beyond the risk issues, some additional perspective on the disease state may help clarify the need for biologic therapy. Psoriasis is a pro-inflammatory disease that not only increases epidermal proliferation, but is also atherogenic. This results in increased cardiovascular disease. Given the comorbidities and the systemic nature of psoriasis, it is critical that physicians treat it appropriately. Moreover, data has shown that biologics may decrease the incidence of heart attacks and strokes, and thus the risk of taking biologic agents may be less than not taking them.
BIOLOGICS 101: FRAMING THE DISCUSSION
The final therapeutic decision to treat psoriasis is often determined by four main factors:
• The dermatologist's interest in treating psoriasis.
• The dermatologist's knowledge of the risk benefit/ratio of each agent, and how the dermatologist frames the conversation.
• Patient comfort level.
In regard to the first point, not all dermatologists regularly treat psoriasis, and it is important in these cases to make the appropriate referrals (see sidebar on page 53). However, for the following points, it is important to have a deep familiarity with the screening protocols. In addition, physicians must be prepared to have a frank conversation with patients and present a fair portrait of safety information to patients.
Objectively, clinical trial data should be utilized to express expectations on speed of response, efficacy over time, and potential adverse event profile.
To alleviate patient concern on safety, it is important to conduct a thorough patient medical history, including malignancy, tuberculosis (TB), Hepatitis B and C, opportunistic infections, recurrent infections, CHF, demyelinating disease, previous psoriatic treatments, and responses both positive and negative to each agent. A personal and family history of lymphoma/leukemia is also important.
After this, the patient should be tested for TB and Hepatitis B and C. Other tests that patients should take prior to initiating a biologic agent are complete blood count (CBC), platelet count, and a SMAC20 comprehensive metabolic panel. Patients should be warned to notify the physician if an infection occurs, stop the biologic and only restart after all symptoms have resolved. Also, physicians should preach the avoidance of live vaccines and discuss timelines for discontinuing the agent if a female patient is trying to conceive. It's also important to tell patients to contact you if they are experiencing any symptoms of cough, weight loss, fevers, night sweats, lymph node swelling, blurry vision, yellow eyes, or grey stool. Also, patients should be re-evaluated every three months initially and blood work and TB testing should be tested annually.
This is a lot of information for patients, which is why it is important to frame the conversation in a way that communicates your willingness to help them and the power of biologic therapy to offer relief. In talking to patients, I tell them up-front that I can help them, that the treatments we have today are far more effective, and I believe in many cases much safer than what was available at the turn of the 21st century, and that it is not a bad time to have psoriasis. I think by asking the preceding questions and eliminating relative contraindications, explaining to them what tests will be obtained and why, and explaining to them that infection is the most likely adverse event and the vast majority of adverse events are treatable. I also explain how effective a drug can be in understandable terms. For example, I might say that 71 percent of patients with psoriasis get 75 percent or more better on etanercept (Enbrel, Amgen) by week 16, or 67 percent of patients on ustekinumab (Stelara, Janssen) get 75 percent or more better by week 12.
Most importantly, during this discussion, it is important to create a sense of the severity of the disease and convey that treatment isn't always easy. I tell patients that they have a chronic immunologic disease and that this is not three weeks of poison ivy. Moreover, I tell them that they will likely have to stay on biologics for many years, because at present there is no cure, but there are meds that can suppress the disease relatively safely. It is also important to impress upon patients that if they stop taking the medication that the psoriasis will likely come back and that when patients start and stop their medicationss sometimes those medications won't recapture efficacy.
THE BASICS OF ACCESS TO BIOLOGIC THERAPY
While it is important to clearly and honestly convey information about the safety and efficacy of biologic agents, having the conversation is just the first step. The treatment process itself also presents its share of difficulties. But with the right approach, treatment doesn't need to be as difficult as it tends to be represented. Nevertheless, physicians and patients must address a number of logistical issues and potential barriers in order to secure biologic therapy.
Arguably the most important factor when it comes to access to biologic therapy is financial in nature: If the patient cannot afford the medication, no amount of evaluation, testing, and explanations about safety and efficacy will matter. Moreover, insurance companies tend to strictly regulate access to biologic therapy by patients. One of the most common barriers insurance companies put up is necessary failure of other therapies prior to initiating a biologic agent. Often, methotrexate is recommended as a first-line agent. However, in the psoriatic population there are many relative and absolute contraindications to methotrexate therapy, e.g., alcohol consumption, diabetes, hyperlipidemia, obesity, women who are planning to get pregnant. Hence, it may be necessary to educate medical directors and assistants of insurance companies to decrease the hurdles placed to notify the physician for patients to obtain the appropriate medication.
Upon prescribing a biologic agent, physicians, patients, and medical assistants need to follow a series of steps to ensure the medications are approved and shipped properly: Most biologic agents are only available through a specialty pharmacy, which is a facility that provides medications that often require special storage and handling that retail pharmacies cannot manage. Since biologics must be refrigerated at all times, they are only available through specialty pharmacies that have the ability to not only store the agents but also ship them on ice, so that the medication stays cool. Commonly used specialty pharmacies include Bioplus, CVS, Caremark, Accredo, Aetna, Express Scripts, Curascripts, and Prime Aid. Given their specialized nature, most specialty pharmacies ship agents directly to the patient or the practice, which eliminates the need for close proximity. Getting to that stage, however, requires communication between the prescribing physician, the patient, and the practice where the patient was prescribed the medication.
First, either the physician or an assistant must complete an enrollment form for a specialty pharmacy. This should include the patient's demographic and insurance information (including blood work, chart notes, previous medication information), as well as a copy of the prescription. Once the prescription is received by fax, the specialty pharmacy electronically submits it for insurance verification. Sometimes the prescription needs to be triaged to another specialty pharmacy due to the patient's insurance, and an Explanation of Benefits (EOB) is generated explaining why they cannot fill the prescription.
All biologic agents require prior authorization (PA) by the insurance company before the medication is dispensed. They want to know what has been tried and failed, i.e. topical therapy, systemic therapy, phototherapy, etc. Importantly, specialty pharmacies may differ when it comes to securing approvals depending on the patient's insurance coverage. Therefore, gaining familiarity with several different specialty pharmacies can be helpful when it comes to securing an approval. It can also save time and frustration if you know which pharmacy is best for passing through approvals.
Once a submission is made to a specialty pharmacy, it can take seven to 10 days to get an answer, after which the medications are generally approved for six months. If denied, physicians can write a letter of medical necessity to the insurance company, detailing why the patient is best suited to a particular medication.
Once a biologic is approved, a patient care coordinator from the specialty pharmacy will contact the practice and the patient to explain benefits and other logistics, such as copays and shipment date. For high copays, copay assistant cards from the manufacturer may be available, so it's important to ask. After this, the specialty pharmacy will then inform the practice of the shipment date; for adalimumab (Humira, Janssen) or etanercept, the medication can be shipped directly to the patient's home. Ustekinumab, however, often ships only to the practice.
Wherever the medication ships, patients should then be scheduled to come to the practice for training on how to inject the medication. While the prescribing physician describes these protocols on the initial visit, often the medical assistant handles the training appointment, which encompasses further discussion regarding adverse events, whether to take the medication while sick, and any other questions the patient may have. In our practice, we send the patient home with literature on injecting, as well. Some biologic manufacturers also dispense pens that “speak” to the patient and walk through the steps for injections. Also, if your practice cannot accommodate time to instruct patients about injection, ambassador programs are available.
STREAMLINE THE PROCESS
Patients tend to have greater fear of biologic agents than the data would suport. In fact, long-term data does not show a cumulative risk; malignancy data with biologically treated patients has been shown to comparable to the population as a whole. When placed in the context of a risk-benefit ratio, it has been shown that the risks of biologic therapy are comparable to placebo, and that between 60 and 80 percent of patients receiving biologic therapy experiences a significant improvement of their disease.
However, despite the convincing long-term data, biologics have still not taken off as perhaps they should. One of the main reasons for this is that dermatologists can become overly taxed in the process of securing insurance approval and obtaining biologics from specialty pharmacies, which admittedly can be a painstaking process. The most efficient method is to have at least one medical assistant become proficient in access. The learning curve can be facilitated by asking each biologic company's drug representatives to help provide information on what is the least burdensome way of obtaining access to their drug. Also, let the patient know that the office will provide this service.
With the right structure in place, administering biologics doesn't have to be a burden for dermatologists and patients.
James Zapata, Medical Assistant at Windsor
Dermatology, contributed to this article.
Jerry Bagel, MD, FAAD, is director of the Psoriasis Treatment Center of Central New Jersey.