PracticalDermatology

This roundtable discussion on prescribing biologics is something I felt was essential. Rather than discuss specific products or considerations related to treatment, the goal is to expose some of the issues regarding perceptions and obstacles to dermatologists as they pertain to not writing biologics for patients with various conditions that may be treated with biologic drugs—not just psoriasis.

Access aside, why are the majority of dermatologists not writing biologics, given all of the data on safety and efficacy for psoriasis, atopic dermatitis (AD), hidradenitis suppurativa (HS), or anything else? Is it really a concern about safety or something else?

Jonathan Weiss, MD: It’s all about comfort level and motivation. Many dermatologists don’t want to be bothered with learning about a new modality of therapy, adapting their practices to the needed changes (biologics coordinators, specialty pharmacies, etc.) or prescribing injectable medications. Some have a fear of the term “biologic,” and some cite concerns about treatments that have not stood the “test of time.”

James Q. Del Rosso, DO: There are a variety of reasons. Some do not want to hassle with the explanations and safety discussions, even with all the data. Others get on their “high horse” about “cost to society” (this is a minimal group but it sometimes comes up).

Andrew Alexis, MD: The time involved in obtaining prior authorizations may be a deterrent to some practitioners who may not have the staffing infrastructure to handle biologics prescriptions. Exposure to biologics during residency training or lack thereof is also a major determinant of comfort level writing biologics in practice.

Scott Drew, DO: I think there is a fear of work flow interruption or an increase of work flow to an already overworked office staff/prior auth nurse. It is certainly easier to write a prescription for triamcinolone ointment and offer a recheck in six months, because some patients might not be aware of more aggressive/effective alternatives. Additionally, among those who didn’t study immunology in residency or during practice, some may find the challenge of mastering the changing understanding of PsO/PsA to be too cumbersome.

George Han, MD: It’s hard to break this idea down into a single item; I think what is often said regarding clinical concerns—potential concerns about safety and long-term unknown effects with novel treatments and inexperience with using these medicines—has been largely debunked. Safety-wise, we have had over 15 years of experience with biologics, and our newer biologics are more targeted and less immunosuppressive than the earlier ones, which have never demonstrated any increased risk of internal malignancy. Some of the newer biologics used in treating psoriasis are even being considered as adjuvant treatments for certain types of cancer, including lung and breast cancer!

We have many new medicines in dermatology coming out and the uptake on these medicines can be quite robust. The injections themselves are really quite straightforward (much easier than intramuscular Kenalog injections, for example). Interestingly, a global study of biologic use (the MAPP study) a few years ago cited some factors such as inconvenience, laboratory monitoring, in addition to safety, as major concerns. Our newer agents are much more convenient and one might argue that an injection every month or less frequently than that is probably more convenient than smearing on ointments twice daily or remembering to alternate calcipotriene with topical steroids to limit long-term side effects of topical treatments. Laboratory monitoring is minimal, with one test prior to initiation as the only requirement for the newer classes of biologics.

So, I think it’s probably some combination of a perception issue combined with the fact that it takes a lot of time to counsel a patient on the treatment options, and even more time to get a medication approved. From a practical standpoint, I think those are bigger barriers than true medication-related problems. It’s not patient inconvenience, unfortunately, it’s a logistical inconvenience in a lot of cases. But if you think about all the hassle that goes into prescribing isotretinoin—iPledge, prior authorizations for the medications themselves, monthly lab monitoring—one really wonders why there are more than 10,000 dermatologists registered for iPledge but yet a minority of dermatologists will prescribe a biologic. Isotretinoin has a side effect rate of nearly 100 percent, twice as high as placebo, with severe AEs of teratogenicity, depression, elevated liver enzymes, SJS, to name a few. The biologics look really good next to that side effect profile, but there’s somehow more stigma attached to them.

What tips would you share with your colleagues for making it easier to prescribe and start patients on biologics?

Dr. Alexis: Understanding that the investment of starting a patient on a biologic pays off in dividends in that the follow-up visits are not only extremely rewarding (e.g., seeing patients who are thrilled about how much their skin has improved and whose lives have been transformed as a result), they are also quite efficient. Having quick follow ups with happy patients certainly contributes to having an enjoyable day at the office!

Dr. Han: Finding a good specialty pharmacy that you can partner with is very helpful. They can help you with the prior auths, get the patient registered into the copay programs, or even help with the manufacturer’s assistance programs in case of repeated denials. They’ll also be helpful in figuring out whether another medicine that is preferred would be easier to be prescribed, but still give the prescriber the final decision. Truthfully, we’re usually able to get our patients on the right medication one way or another, and certain states have step therapy or prescriber prevails laws, which can help. It’s hard the first few times, but in a world where I sometimes get prior auths for prescribing ketoconazole cream or fluocinonide ointment, I don’t see it as an unreasonable additional burden.

Dr. Drew: Find a single specialty pharmacy, and stick with them. Have them navigate all of your biologic prescriptions, and they will come to know your practice patterns and patients; dedicate staff to your biologic prescriptions. You don’t need a biologic coordinator, but you do need your staff to be educated and on-board, so that they can answer patients questions. That education can be done by the doctor or by reps/Medical Science Liaisons (MSLs) from the various biologic pharma companies. I would also remind new prescribers that the first one to five prescriptions of any new Rx by an office is usually frought with difficulty, so I would encourage a new biologic writer not to be discouraged by a few denials at the beginning of their biologic prescribing. It gets easier over time. I would also recommend to forge a relationship with a colleague to be a “biologic buddy”—a derm you know/trust who can help you navigate the initiation into a biologic practice.

Dr. Del Rosso: Provide guidance on what info needs to be collected up front in history, extent of signs and symptoms, including how patients are affected, all prior treatments, and explanation of why a therapy is selected. Also, a few prior authorization letter examples are helpful. Staff training of the right person at the office to work with. Have a really good field and dedicated access person who works well with reps and MSLs if you go this route. Personality conflicts in the field within a company are major problems that home office does not see. Most field access reps are not good and basically an overhead drain, and are in and out (have no accountability to bottom line which is never good).

Dr. Weiss: Start by talking to colleagues who prescribe biologics frequently. Look at the results that patients get on biologics. Review their safety profiles. Then, ask to speak with some of the MSLs or other medical personnel at the pharma companies. Find a specialty pharmacy that will help you handle prior authorizations (biologics reps generally know these) or prescribe the biologics from companies that make filling the prescription seamless.

Is there a perception that dermatologists are leaving prescribing biologics to mid-level practitioners or to rheumatologists? And why?

Dr. Han: Unfortunately, the idea of giving the less-desirable tasks to someone else is a common theme in almost any dimension of life. In thinking about a busy dermatology practice, the idea of a 30-minute consultation for a new patient with moderate to severe psoriasis (which is, I think, about how long it takes to have a thorough consultation and decide on next steps) isn’t realistic for many. Whenever my medical assistant sees a new psoriasis patient on my schedule, she knows to already start trying to get us moving quickly because I’ll get a little behind. But these patients deserve it! They’ve been dealing with their psoriasis, in many cases, for decades, getting sporadic treatment. Getting these patients better is extremely gratifying! These are often my most appreciative patients, and the follow-up visits for a patient on the right biologic are often very fast, so you make that initial time investment up in the longrun. I won’t get into the weeds about cosmetic practice vs. medical dermatology, but we should really own inflammatory skin diseases as that, in my opinion, is what really makes dermatology special and necessary.

Dr. Drew: I believe that is accurate in some areas, where the physician is concentrating on surgeries, pathology, or cosmetic procedures, while leaving the routine derm to extenders. It is important somewhere along each patient’s biologic journey that the dermatologist is with the patient to discuss safety/efficacy, the paradigm shift to a “needle-based” therapy , rather than a pill or cream, and to assure the patient that biologics are cutting edge, current state of the art therapy. If we relegate our patients solely to our extenders, we cannot be surprised if access to them is made easier by state legislatures.

Dr. Del Rosso: In many cases, the dermatology “mid-levels” are easier to get access to in order to influence them on prescribing considerations, especially those that are loosely supervised. These situations do happen in some cases, depending on the office and the “mid-levels” involved.

In the case of rheumatologists, a lot of dermatologists are fully “gun shy” about psoriatic arthritis and refer immediately to rheumatology. In fact, dermatologists can pick up on undiagnosed cases of psoriatic arthritis and initiate therapy for both cutaneous psoriasis and psoriatic arthritis with a biologic agent and still refer to rheumatology when necessary for more advanced evaluation and management, if needed. This takes education and chipping away at it step-by-step, as there will be a lot of slow adopters.

Dr. Weiss: Some dermatologists do leave the prescribing of biologics to Advanced Practice Practitioners (APPs, latest preferred terminology by PAs and NPs) or rheumatologists, but these are the same dermatologists discussed in the first question above. They simply don’t want to learn about the biologics or take on the types of patients who need them. Some of it is fear of the unknown/unfamiliar, and some of it may be laziness or a lack of desire to expand their horizons. Most APPs are younger, possibly more receptive to pharma, and willing to take on new challenges.

Dr. Alexis: Similar to my response to the first question: Some dermatologists may feel that the time spent navigating prior authorizations and coordinating the initiation of biologics is beyond what they can handle themselves in the context of a busy practice and are therefore inclined to delegate this.

If not biologics, then what is the preferred treatment for psoriasis and why (besides access)?

Dr. Han: I think there are some cases where patients can be managed with topicals, but unfortunately, it’s been shown time and time again that patients with severe psoriasis who really should get a systemic treatment are being managed with only topicals or not at all. Phototherapy is useful and for some patients without any joint disease, could be reasonable. I don’t find much place for a lot of the oral medications. The older ones (methotrexate, cyclosporine) are not as safe as biologics, and the newer option (apremilast) is only useful in certain situations, such as scalp psoriasis and/or palmoplantar psoriasis. I think some oral medications on the horizon may change that dynamic a bit, though.

Dr. Weiss: There are no superior treatments currently available for psoriasis over the biologics in terms of efficacy and safety. However, some prefer methotrexate because of familiarity, despite its inferior safety profile and inferior efficacy.

Dr. Alexis: A safe oral agent, such as apremilast, is a good fit for patients who are closer to moderate than severe in the psoriasis spectrum. The lack of monitoring and favorable safety profile are key advantages, as well as the ability to treat psoriatic arthritis and scalp psoriasis.

Dr. Del Rosso: Oral apremilast grabs a lot of the “tweeners” between topical therapy and biologic therapy. Topical therapies are still very important for localized disease and persistent lesions. We still have cyclosporine and methotrexate at our disposal, but they are not usually preferred. Phototherapy (NB-UVB) is helpful in some cases.

Dr. Drew: Many derms still prescribe methotrexate, cyclosporine, and phototherapy rather than biologics. Excuses I hear/read are “That’s how I was trained,” “It works,” “Biologics are too expensive,” and occasionally, “I don’t understand biologics, “It’s too hard to get biologics,” and most often, “My patients won’t take them.” I think it is our job to provide information to patients, and if we do it properly, our patients will take biologics.

What are some factors that drive the decisions to start TNF inhibitors vs IL-17, IL-17R, and IL-23 inhibitors?

Dr. Drew: I think starting with TNF Inhibitors is easier for many doctors because there is an abundance of safety and efficacy data, and this eases their comfort level. In this schema, TNFs can become a “gateway biologic,” enabling trials of other more aggressive therapies. Somewhat surprisingly, there are some that believe the new agents still have some safety issues to prove, remembering the Raptiva experience.

Dr. Del Rosso: Anti-TNFs can be used for psoriasis and psoriatic arthritis, and most also will help hidradenitis suppurativa. The IL-17 inhibitors are very effective and safe overall. IL-23 inhibitors are about the same in efficacy but I have thus far favored IL-17 inhibitors as they kick in faster.

We can split hairs on efficacy data, but in reality all these drugs work very well in most people. Whatever gets through easiest is usually the winner, unless there are major cautions or prior failures.

Dr. Weiss: The main issues are familiarity (longest history on the market) and perceived safety when it comes to psoriasis vulgaris. Some prefer TNF inhibitors because of potential to treat comorbidities, especially psoriatic arthritis. There is also the fact that TNF inhibitors have 11 or more indications, so a large number of prescriptions have been written with no new safety signals. But, when it comes to efficacy in psoriasis vulgaris and reported safety to date, the IL-17, IL-17R and IL-23 inhibitors appear to have superior efficacy with no unexpected safety signals.

Regardless of your position as a dermatologist, it is important to have respect for new treatments and realize that we will not know the full effects of their benefits and risks for many years. They should be prescribed when appropriate but also within their indications and guidelines. To this point, TNF-inhibitors and ustekinumab appear to have stood the “test of time” in terms of safety. IL-17/IL-17R inhibitors and IL-23 inhibitors appear to be on the way to that status.

Dr. Alexis: Some factors include the a.) presence or absence of psoriatic arthritis (favor TNF-inh or IL-17A-inh); b.) comorbid conditions such as inflammatory bowel disease (favor TNF-inh or IL-23-inh), CHF (favor IL-17, IL-17R, IL-23-inh); c.) disease severity (favor agents with greatest efficacy), d.) patient preferences for dosing frequency or speed of response; and e.) previous therapies.

Dr. Han: We are lucky to have a large number of good choices. Certainly, a major deciding factor will be the presence of psoriatic arthritis, which pares down the choices right away. The general feeling is that the TNF-alpha inhibitors and IL-17 inhibitors are the best for joint disease but IL-12/23 or IL-23 inhibition may provide adequate coverage in some cases. Some of the TNF-alpha inhibitors have started to show an increased risk of NMSC, specifically SCC, so I find that I’m reaching for those less, in addition to the fact that there’s more lab monitoring, and some of the medications have a higher rate of anti-drug antibodies leading to secondary loss of response. In this regard, there are some carve-outs where certain TNFs may be particularly useful; I’ve reached for certolizumab-pegol for both women who are family planning and in patients who develop secondary non-response to a TNF-alpha inhibitor, as the rates of antibody formation are rather low for that medication.

A lot of times, it comes down to patient preference in terms of dosing frequency and balancing comorbidities, such as CHF or IBD, and in that regard, a lot of the newer medicines provide less to have to think about and favorable dosing regimens as well.