Isotretinoin, shown safe and effective when used appropriately for the treatment of acne, is a drug with a persistent image problem in some circles. Ironic, considering that the drug is indicated for the treatment of severe, recalcitrant, nodular acne—the kind of acne most likely to result in both physical and emotional scarring. In fact, says Richard G. Fried, MD, PhD, isotretinon, “is the single most effective treatment for this kind of acne.” It remains the treatment of choice for patients with refractory acne at high risk for acne scarring because it is often the best therapy to efficiently resolve severe acne and thereby reduce the risk of scarring. Dr. Fried urges clinicians to be more sensitive to the impact of severe acne and be prepared to intercede from a therapeutic standpoint. “It is critical that we identify the signs of physical and emotional scarring in the patient and then move in an efficient, rapid, unencumbered, and organized fashion. We should move patients from the isotretinoin decision to getting the first dose of isotretinoin in their mouth as quickly as possible,” Dr. Fried says. A new pharmacy service program, The Promius Promise, strives to support rapid therapeutic initiation through a comprehensive range of patient and practice support services. Here’s a look at the role of isotretinoin in acne care today and the soon-to-belaunched program.

Real World Use of Isotretinoin

Accepted use of isotretinoin in the real-world setting has expanded to include not only nodulocystic or scarring acne but also acne of any severity that is refractory to other treatments or acne that is causing significant emotional distress, Dr. Fried observes.

Assessing emotional scarring or the risk for it can be the most significant challenge for many physicians who treat patients with acne, Dr. Fried acknowledges. “The data remain robust that patients with severe acne are at increased risk for anxiety, depressive disorders, OCD, and functional impairment at home and the workplace—interpersonally, and sexually.” At the same time, he notes, the data further indicate that the relationship between the severity of acne and the extent of its emotional impact is not necessarily linear. For example, he says that dermatologists should not assume that the patient with moderate disease or “just a few scars” will be less affected than the patient with more extensive involvement.

When it comes to estimating the effect of acne on any given individual, Dr. Fried insists, “The truth is we don’t know.” Furthermore, the duration of that effect is hard to ascertain. In his book Healing Adult Acne, Dr. Fried addresses the phenomenon of “Phantom Acne”; adult patients who had acne in adolescence, acne free for many years, may continue to react to stimuli such as visual inspection or touch as if they have active acne lesions.

Directly questioning patients about the emotional impact of their acne is one option, but it is not always that reliable, according to Dr. Fried. Male patients, in particular, may be unlikely to explicitly state that they experience emotional side effects from acne. To improve the likelihood of receiving an honest response, consider violating the two-second eye contact rule. Looking into the patient’s eyes for three to four seconds after asking a question may make them just unsettled enough to answer honestly. Eye tearing, head shaking, or downward gaze can be a clue to their emotional discomfort.

There are other indicators to consider when assessing a patient’s emotional state, he says. For one, Dr. Fried observes, an increasing number of adolescent male patients have asked about camouflage for acne. This, he says, can be a sign that they are feeling the burden of their disease and looking for “protection” from the negative psychosocial effects of their acne.

Also look at their body language and clothing. These include hats, hoods, slumped posture, difficulty maintaining eye contact, downward gaze, or inability or refusal to make or maintain eye contact. Patients emotionally affected by acne may also be irritable, emotionally labile, or overtly hostile.

Why Isotretinoin

Research is confirming what isotretinoin taught us years ago, Dr. Fried insists, “Isotretinoin is one of the greatest teachers we have had in acne.” New findings continue to emerge about inflammation, inflammatory peptides, immune response, and other aspects of the complex pathogenesis of acne that usually all resolve via isotretinoin therapy.

Now we know “you don’t have to kill anything to treat acne,” Dr. Fried observes. Rather, by “getting at the root of the pathogenesis of acne—abnormal keratinization and inappropriate inflammation—isotretinoin allows us to fix the fundamental problems of acne. When you address that fundamental problem of acne, the normal commensal P. acnes no longer overgrows, and thus the TLR activation and other factors in the pathogenesis of the disease are halted.”

As a synthetic vitamin A derivative, isotretinoin targets acne in a “natural fashion,” according to Dr. Fried, “correcting the problem without altering the natural balance of bacteria and fungi in the body, as we do with antibiotics.” Similarly, it does not influence hormones. “When you look at it from the Hippocratic oath perspective of ‘Do no harm,’ isotretinoin can be a powerful contender in that arena,” Dr. Fried adds.

Let us not forget that isotretinoin does, of course, come with its own set of concerns, Dr. Fried states.

“As long as pregnancy is avoided, as long as patients have normal liver function, as long as the patient does not have hyperlipidemia, and as long as there is not excessive alcohol or drug use, isotretinoin is extremely user-friendly,” Dr. Fried maintains, noting that lower-dose therapy, as has become popular in recent years, may be considered.

Persistent Challenges

Although isotretinoin offers the best probability of cure or prolonged remission of acne in a very high percentage of patients, there remains some hesitation to prescribe. Teratogenicity during first trimester of pregnancy, dyslipidemia, and dose-related xerosis aside, many prescriber concerns are rooted in the persistent myths regarding depression, suicide, and inflammatory bowel disease. While generally unfounded, lengthy patient discussions and fears of litigation can be obstacles to prescribing, Dr. Fried suggests. This societal folklore, though unfounded by science, seeks to link isotretinoin to depression, inflammatory bowel disease, and unavoidable problem pregnancies. Some prescribers may not want to invest the time in education aimed at countering these widespread and persistent myths. “As I’ve noted before,” Dr. Fried says, ‘Scientific data pales in comparison to well-orchestrated media sensationalism.’”

Adding to the challenge, the Internet has become a source of misinformation and, more troubling, litigators actively recruiting plaintiffs. Yet, there are two sides to the issue, Dr. Fried warns. “If a clinician believes they are protecting themselves and their practices by not prescribing isotretinoin, they should consider the risk of scarring associated with undertreatment of acne,” he suggests. “Google ‘acne scarring,’ and there are also numerous links to litigators.” More than fear of litigation, he suggests, good medical practice argues against undertreatment.

Sensible and appropriate prescribing remain essential in the current setting. “I believe that pregnancy prevention programs make good sense,” Dr. Fried reiterates. Furthermore, he highlights the need to educate patients, parents, families, and significant others that isotretinoin should never be taken without physician supervision.

“If we do accept the initial assumption that we are dealing with a population at risk, anything we can do to expedite the process to get patients onto medication even a tiny bit sooner, statistically speaking, is going to save lives,” Dr. Fried says. Yet, data show that in 2010 more than 400,000 of the one million-plus prescriptions for isotretinoin were denied.

Any dermatologist practicing at the time of its implementation recalls the overwhelming challenges of iPledge’s initial inception in 2006; there was a documented decline in the number of isotretinoin prescription writers in the wake of the program’s launch. Over the next two years, a movement largely spearheaded by Ranbaxy Laboratories (which markets Absorica), resulted in a more streamlined program, Dr. Fried observes. Many practices and patients have found the second iteration of the program more manageable, he feels, and it is not a significant barrier to prescribing.

Nonetheless, there remain certain requirements on the prescriber and patient, and non-adherence to firm timelines that may translate to delay in treatment or a discordance between the number of prescriptions ordered and the number filled.

A New Solution: The Promius Promise Program

A new program available through Promius Pharma (which is launching Zenatane (isotretinoin) Capsules), The Promius Promise Program pharmacy service may further streamline the process of isotretinoin prescribing and iPledge compliance, Dr. Fried believes.

Launching along with Zenatane, which recently received FDA approval, The Promius Promise Program aims to provide Zenatane to eligible patients in the US within 24 hours, at reduced or no out-of-pocket expense and with no shipping fees. Partnering with an accredited iPledge-certified, US-based pharmacy, the program offers educational support for patients and assists with every aspect of iPledge program compliance.

Excited about the prospects for the program, Dr. Fried says that it is a potentially emotion- and life-saving program that will bring important care to patients. In addition to preventing delay in therapeutic access and preventing patient drop out (Dr. Fried points out that some patients who encounter any obstacle to access, including but not limited to, missed deadlines, will simply drop out of treatment), the program may also improve staff morale. That’s an important consideration for many busy practices, Dr. Fried stresses. Staff get bogged down daily with phone calls about generic substitution, non-formulary call-backs, patients missing their time windows for pregnancy testing, Dr. Fried says. Sometimes they can address issues directly, other times they need to schedule the patient for in-office appointments. The new program, theoretically, will remove this burden on staff.

At the same time, patients who feel that the program is a partner in care may become increasingly empowered, Dr. Fried predicts. Empowered patients generally tend to be more adherent and active in care. Furthermore, they are less likely to become frustrated and to target staff with their frustration, he adds.

Toward Efficiency and Improved Outcomes

Isotretinoin is an effective and important treatment option for acne, Dr. Fried maintains. It offers proven efficacy, reliable safety when prescribed appropriately, and the potential for long-term remission. By reducing the burden of nodulcystic acne and reducing the risk for acne scarring, isotretinoin can improve the emotional health of patients. In some cases, the impact of therapy is “like taking a wilted flower and giving it water,” Dr. Fried says; patients experience a return of self confidence and emotional health that can manifest in improved affect, straighter posture, bright eyes, etc.

Nonetheless, access to treatment has been hindered by practical limitations as well as patients’ and prescribers’ perceived but frequently unfounded concerns. iPledge, which initially created additional and challenging work for practices, has since evolved to provide a framework for appropriate prescribing of isotretinoin, but the program continues to saddle practices and patients with certain responsibilities. The new Promius Promise Program, by partnering with patients and practices, may further streamline the iPledge compliance process, help patients navigate insurance coverage issues, overcome certain cost-related access barriers, and expedite the delivery of therapy to patients. The result could be happier, better managed patients and more efficient, lessstressed practices.