For what diseases is it best to try traditional drug therapies first, and are there any instances in which going straight to the biologic is reasonable? Doctors and patients want the latest and greatest, but payers want better safety and efficacy data.
Abstract
Arguing that traditional therapies often are not worth the time and money, some moderately to severely ill patients and their physicians have sought to use biologics first line – particularly for diseases where some older drugs can involve adverse effects. Until payers see evidence to show superiority of biologics, however, use of step therapy with conventional drugs is not going away.
Step therapy is a long-established strategy intended to ensure the use of the most clinically sound and cost-effective drug. Along with prior authorization, quantity limits, and pharmacy benefit tiering, step therapy also is an accepted approach to the challenge of balancing clinical efficacy and cost-effectiveness in the treatment of patients with chronic and other conditions.
But what happens when biologics are thrown into the mix? Confusion, concern — and yes, some conflicts — inevitably arise. With respect to the requirement that a traditional therapy (or even a specific biologic product) be used before an injectable is employed, physicians have voiced concern about the efficacy of older therapies in patients with certain moderate to severe chronic diseases. Biologics manufacturers caution that specialty drugs often are not interchangeable, and payers assert that evidence of long-term safety and efficacy of biologics often is lacking, to say nothing of the costs involved, which cannot be ignored. Some 125 biopharmaceuticals had U.S. Food and Drug Administration approval by the end of last year, with 349 more in phase 3 trials or undergoing FDA review. For third-party payers, this avalanche of new therapies comes at a time when employer purchasers are trying to stabilize their costs of providing healthcare benefits.
And in what seems, on the surface, to be a replay of the same scenario seen across managed care in the 1990s, physicians charge that step protocols result from payers being too focused on the bottom line and ignoring the complexities of caring for chronic conditions like psoriasis and rheumatoid arthritis. For their part, health plan medical and pharmacy directors and pharmacy benefit management executives say their policies are grounded in evidence — or the lack thereof. And policy experts say this is yet another example of how the American healthcare system has difficulty addressing complex pharmacoeconomic and medicoeconomic issues.
PSORIASIS: A CASE STUDY
An example of how this is all playing out is psoriasis. Some of the medications most commonly used to treat chronic psoriasis, including methotrexate and cyclosporine, are well known for their side effects: for methotrexate, hepatotoxicity and bone marrow suppression, and for cyclosporine, renal problems. The threat of accumulated toxicity often requires physicians to monitor patients carefully and to rotate therapies, a strategy that sometimes can cause disease flares. Some of the dermatologists and rheumatologists who treat patients with severe disease express strong enthusiasm for the new biologics approved to treat psoriasis — alefacept (Amevive), efalizumab (Raptiva), infliximab (Remicade), and etanercept (Enbrel) — the last two of which, along with adalimumab (Humira), are also approved for treatment of psoriatic arthritis and rheumatoid arthritis.
“Clinicians have a sense that policies are somewhat arbitrary and are not always rooted in ... the subtleties of using biologic therapies,” says Bruce E. Strober, MD, PhD, of New York University School of Medicine.
PHOTOGRAPH BY CAROL SEITZ
Some of these physicians object to payers’ use of step therapy-type strategies for the biologics, though they will concede that the cost of these medications alone precludes them from being used indiscriminately. Given the toxicity profiles and monitoring requirements of the main nonbiologic medications for psoriasis (and psoriatic arthritis, a suspected sequela of psoriasis), it’s not surprising that physicians are turning to the biologics with enthusiasm when a patient’s case warrants it.
Classic DMARDs for the treatment of psoriasis can involve potentially severe complications, leading Craig Leonardi, MD, of Saint Louis University, to question whether starting with biologics might be the right thing to do for some patients with moderate to severe disease.
To put things in perspective, says Craig Leonardi, MD, a solo dermatologist and a clinical associate professor of dermatology at Saint Louis University, one has to understand the choices patients and dermatologists faced with regard to psoriasis treatment before biologics came onto the scene. “Functionally,” Leonardi says, “we had three medications available: methotrexate, cyclosporine, and acitretin. If you’re a young woman you can never be on acitretin, unless you can wait three years to get pregnant, so most women simply don’t get that pill. So then, you’re looking at methotrexate and cyclosporine, both of which involve potentially severe complications. Cyclosporine interacts with many other medications a patient is likely to be taking, and if you drink any alcohol, you should not be on methotrexate.
“Then you have phototherapy,” he continues, “which has to be performed three times a week in a doctor’s office. That becomes very challenging and impractical for many working people.”
For many patients, says Leonardi, — a prolific researcher whose 600 patients make up one of the largest dermatology practices in the country — the new biologics have been a godsend. But, he is quick to add, “Right now, we have a fair amount of interference from the insurance industry.”
To Leonardi, the requirement on the part of some health plans that patients must have been on two, or sometimes even three, different non-biologic treatments before a biologic therapy is approved is unreasonable, as was the requirement by one West Coast-based plan that a patient needed to have 30 percent of body surface area covered with psoriasis before qualifying for biologic treatment. That policy — which eventually was changed to a Psoriasis Area and Severity Index (PASI) score of 10 or greater after protest by the National Psoriasis Foundation — was an example of how payer policies, in Leonardi’s view, lack concern for patients: “None of the clinical trials ever started with patients with 30 percent. The trials worked with patients with 10 percent or more.”
Fiona Wilmot, MD, MPH, director of medical policy, pharmacy & therapeutics, and transplants for San Francisco-based Blue Shield of California, says payers are not trying to be arbitrary — they just need evidence. “Step therapy is an evidence-based decision,” she says, suggesting that questions about the long-term safety and efficacy of newer therapies in patients with chronic disease will take time and experience to answer. Until then, she says, the requirement that non-biologics be tried first is not unreasonable: “The psoriasis drugs were studied as rescue therapies in patients who had failed conventional treatments.”
Formulary consultant Renee Rizzo Fleming, RPh, MBA, a former managed care pharmacy director, thinks health plans are flexible but should “have a greater appreciation of you as an individual patient.”
PHOTOGRAPH BY FOREST McMULLIN
NO EASY ANSWERS
At the very least, “The notion of step therapy becomes a little more challenging with biotech,” says David Calabrese, RPh, MHP, vice president of clinical services at Worcester, Mass.-based Med-Metrics Health Partners, one of the only not-for-profit PBMs in the country. “Traditionally, step therapy developed in therapeutic classes of oral drugs where you had multiple entries within certain categories, a fair amount of competition among those products, and evidence suggesting comparability among entities. Step therapy became a more preferential alternative to preauthorization in these categories, because it offered the ability to decrease the administrative burden for physicians, pharmacists, and patients while still accomplishing virtually the same objective.”
With biotech, though, it’s more challenging, he says, because step therapy can involve not only a progression of therapies from traditional to biologics, but also a progression from one biologic agent to another.
“It’s the exception and not necessarily the norm to find opportunity for the same type of competition and therapeutic similarity. In many biotech categories, you have one or two biotech drugs competing now, and they’re not necessarily interchangeable,” he says.
Blue Shield of California employs step therapy for treatments for psoriasis and rheumatoid arthritis. Making the concept of step therapy work with regard to the use of older drugs and biologics is a challenge, says Wilmot, given the lack of true comparative data. “When new drugs come out, there are no data comparing the newer drug regimen with currently accepted therapies. I’d like more data to help guide us.” Further, she says, “If we receive a request for use of a biologic agent as a first-line therapy in a patient who has never tried phototherapy or other disease-modifying agents, then we will review this request to see if there are specific facts of this case that warrant an exception to the usual treatment guidelines, and if not, we will apply step therapy.”
For health plan medical and pharmacy directors, Wilmot says, the landscape for biologics can be amorphous. “Health plans are not in the business of denying care that is helpful to patients, and it is important for physicians and advocacy groups to understand the role of evidence in coverage decisions, which may include step therapies. If the evidence does not support first-line access to biologics to all patients without restrictions, then it is not realistic to expect the health plan to advocate this type of coverage. Our P&T committee looked at this very carefully, and said the evidence isn’t there for it.”
Regardless of the challenges, third-party payers say they want to partner with thought leaders and specialists to come to consensus on what the evidence base should be. Calabrese, for instance, says MedMetrics will do what it can to meet employers’ and health plans’ medication management goals. “We are a PBM, so we support a variety of different clients. We’re very supportive of step therapy as an effective means of managing chronic illnesses in a number of categories. We are, however, very conservative in our approach to the biologics. We want to go beyond simply a ‘one-drug-versus-another’ thought process, and ensure that a patient is an optimal candidate who will benefit from a biologic agent, and that these drugs are being prescribed in accordance with current clinical evidence and best-practice standards.”
MEETING HALFWAY
Physicians at the forefront of these issues say they can understand the concerns, but to many it appears that those concerns override clinical sense. “I truly believe that dermatologists, who tend to be risk-averse, do not want to give biologic therapy irrationally and inappropriately to patients who do not need it. And if left to their own wares, dermatologists would appropriately use therapies —whether they be conventional medications, ultraviolet therapy, or biologics,” says, Bruce E. Strober, MD, PhD, associate director of the dermatopharmacology unit at New York University School of Medicine. “But, clearly, there are instances where one drug is appropriate and another is not. In some cases, a patient should be on etanercept, but there are other instances where a patient shouldn’t be, or can’t tolerate it, or there is a contraindication.”
“We want to ensure that a patient is an optimal candidate who will benefit from a biologic agent, and that that these drugs are being prescribed in accordance with current clinical evidence and best practices.”
— David Calabrese, RPh, MHP, MedMetrics
Strober, who has presented at several conferences on the topic of step therapy and biologics with regard to psoriasis and psoriatic arthritis, believes the process is less about evidence than it is about cost containment. “I believe that payers are simply attempting to save money,” he says. “Payers don’t take this approach with less-expensive therapies for psoriasis.”
“I am not blind to the issue of cost containment,” he continues. “I understand the pharmacy director has to balance the bottom line, and for that reason, wants to be sure that certain biologics are being appropriately used. And I feel we’re going to meet halfway.”
What is halfway? In response to the question, Strober replies, “Pharmacy directors should be open to high-level dialogue with physicians like me, so that reasonable guidelines and policies can be set.”
Wilmot, at Blue Shield of California, thinks that dialogue does exist, but reiterates that “Evidence is the most important aspect.” Strober’s feelings would suggest that plans and payers still have some challenging work ahead to meet halfway: “Right now, clinicians have the sense that policies are somewhat arbitrary and not always rooted in clinical experience and knowledge of the subtleties of using biologic therapies.”
For dermatologists, says Strober, “One issue that is acutely problematic is the frequency with which we need to reauthorize medications — almost every three months with some health plans.” The complexity of the reauthorization process, combined with the fact that every health plan has differing requirements, makes reauthorization a “Kafkaesque” proposition, he adds. Moreover, he says, “Reauthorization is superfluous, as dermatologists would not want to continue an ineffective therapy. The assumption should be that if the patient is continually being prescribed a drug, it is working.”
Many third-party payers would contend that current step-therapy protocols for many biologic therapies are not arbitrary at all. Thorough literature searches are routinely performed and whatever clinically sound and relevant information is available for the biologics in question is used in determining step-therapy protocols. However, for many biologic therapies, there is a lack of long-term evidence regarding efficacy and outcomes when biologics are used in place of traditional therapies or when one biologic is used in place of another. To bridge the gap between physician perception and payer reality, a great deal more dialoguing will have to take place between insurers and physicians before routine industrywide norms can be established.
“I truly believe that health plans are willing to have that dialogue and to work with specialists to reach consensus on practice guidelines,” says Renee Rizzo Fleming, RPh, MBA, an East Amherst, N.Y.-based managed care pharmacy consultant whose firm, PRN Managed Care Consulting Services, works with health plans on formulary issues. “Practice guidelines cannot be developed in a vacuum. The health plan must work hand in hand with the specialists when developing the guidelines to ensure that everyone is on the same page.”
TOWARD SECOND-GENERATION STRATEGIES
All those interviewed agree that one element missing in this debate is the ability to rely on any kind of broad policy or societal consensus on what is reasonable in coverage for biologics for chronic conditions, such as psoriasis, psoriatic arthritis, and rheumatoid arthritis. In the absence of such a consensus, the issues inevitably get sorted out at the clinician-reimbursement level, which tends to tip the process toward tension and conflict. But some leading industry observers don’t see the situation as inherently negative.
As messy as this process can be, the discussions taking place about step therapy today are useful in moving the process toward more consensus, says one policy expert.
“Every society has to find ways to balance the competing virtues of open access to any product, regardless of its cost and the extent of scientific uncertainty, versus the virtues of affordability and of getting insurance to the uninsured. That process of balancing is difficult and thankless, but essential,” says James C. Robinson, PhD, Kaiser Permanente Distinguished Professor of Health Economics at the University of California. “And it needs to happen, realistically, at multiple levels. The government has a role to play through the Food and Drug Administration; the Centers for Medicare and Medicaid Services has a role to play based on its position as a reimbursement trend setter; private health plans have a role to play; physicians have a role to play. Patients, through their own choices with respect to health insurance, have a role to play.”
But Robinson insists that the kinds of dialogues taking place now about step therapy and biologics are moving the process forward. “There are flaws at every level of the system,” he adds, “but no one has convinced me there’s any better way.” Ultimately, he says, the creation of consensus-based clinical guidelines will provide a path toward a consensus everyone can live with.
Robinson sees step therapy for biologics as one of a series of “first-generation strategies” that include traditional utilization-control techniques now in place among payers: preauthorization protocols, tiering of pharmaceutical benefits, the imposition of copayments on patients, and the use of PBM-based pharmacy management. All these strategies represent early steps in getting a grip on the issues, he says. Second-generation strategies will include price negotiations by purchasers and payers with manufacturers and the implementation of clinical guidelines, as well as “bioequivalents and multiple branded products within the same category.”
Over time, Robinson foresees more consistent health plan policies, formulary management, and benefit designs — “that is, more sophistication on the plan side.” And on the physician side, he foresees “greater transparency, including the development of clear criteria for off-label use, as well as clear reporting and adherence to evidence-based clinical guidelines.”
And that may be where physicians meet payers in the middle, considering payers’ emphasis that their decisions are based on clinical evidence, not cost. As the body of literature for or against the use of certain therapies in specific circumstances emerges, medical society guidelines are likely to follow. Getting there will take time and a willingness among all parties to compromise and communicate.
“People are making progress,” says Robinson, but then, I’m generally an optimist about everything.”