The specialty of Medical Dermatology has been in a renaissance for the last decade or so because of the development of many new injectable drugs for some common complex diseases such as Psoriasis, Psoriatic Arthritis, and Atopic Dermatitis, but also for some lesser known entities which we will discuss later.
The injectable drugs for the most part are known as Biologics. Biologics are complex proteins, usually monoclonal antibodies, that are synthesized in molecular biology laboratories. Mammalian cell cultures produce high levels of the desired protein. Then sophisticated biochemical engineering techniques are used to humanize the protein so that it is not immediately rejected when injected into the human body.
Initially, most of the biologic drugs were developed to treat Rheumatoid Arthritis followed by the similar but less common Psoriatic Arthritis. When dramatic improvement was observed in the skin of patients who also had psoriasis, development of new drugs shifted toward treating moderate to severe psoriasis first.
We now have so many new drugs for treating psoriasis, which affects 2-3% of people in the US, that it can be difficult to decide which one to use first, second, or third when a new patient comes to the clinic for consultation.
In this report, I will briefly highlight what is new, unique or special in the last 2 years in the field. I am speaking from my own personal experience and opinions. I will use brand-names because they are most familiar to readers and easier to spell and pronounce. There are really no generic competitors at this time, but biosimilar drugs may appear on the market in the next few years as patents expire and legal entanglements are settled.
Enbrel, one of the first biologics for psoriasis, a tumor necrosis factor inhibitor (TNFI), became the first biologic to be approved for children of 4 years and older.
Stelara, the only Interleukin 12&23 inhibitor on the market, was approved for children of 12 years and older (maintenance injections every 12 weeks).
Tremfya, became the first Interleukin 23 only inhibitor on the market with maintenance injection frequency of every 8 weeks.
Ilumya, became the second Interleukin 23 only inhibitor on the market with maintenance injection frequency of every 12 weeks.
Humira, also one of the original TNFI biologics for psoriasis, is now approved for an astounding 10 indications. In the last 2 years, Uveitis, an autoimmune inflammation of the eye, and Hidradenitis Suppurativa, a devastating pustular and scarring skin disease (covered elsewhere on this blog) were added to the list. Moreover, the diluent for the injection was made free of citrate which reduced the volume and pain of injection, a significant improvement for some patients.
Cimzia was approved for psoriasis with monthly maintenance injections. It is unique as a TNFI because it is PEGylated and Fc-free. These features allow it to show negligible to low transfer of Cimzia through the placenta and minimal transfer to breast milk. Thus, it may become the biologic of choice for women who need to continue treatment for severe disease through pregnancy.
Interleukin-17 Inhibitors: Both Cosentyx and Taltz were proven to be quite effective for Psoriatic Arthritis and approved for that indication in addition to psoriasis. Both drugs were shown to slow the progression of joint destruction over time.
Siliq also inhibits Interleukin-17 by a different mechanism. It antagonizes the IL-17A receptor which may also block other IL-17 subtypes. It was approved for patients with moderate to severe psoriasis who have failed to respond well to other systemic therapies. There is a warning in the package insert about suicidal ideation and behavior which has occurred in patients treated with Siliq.
Xeljanz is an oral drug that was recently approved for psoriatic arthritis. It was previously approved for rheumatoid arthritis. It is a JAK-inhibitor that works similar to a biologic drug. However, it was not approved for psoriasis. We could use it in a patient who has both psoriatic arthritis and psoriasis.
Enstilar is a newer topical foam which is a fixed combination of calcipotriene and betamethasone 0.005%/0.064%. I have found it to be the most effective although expensive topical for resistant psoriasis plaques. It may be used in combination with above-listed biologic medicines.
Halobetasol is an old super-potent topical steroid that was typically dispensed as a 0.05% cream or ointment. It is now available as Bryhali, a 0.01% lotion that is safe and effective for psoriasis and less likely to cause thinning of the skin (atrophy).
Dupixent, an Interleukin-4 Receptor Alpha antagonist, was approved for the treatment of adult patients with moderate to severe disease who have not responded well to prescription topical therapies. The drug is working well in our patients so far, and the only side effects noted have been conjunctivitis and pain on injection.
Eucrisa (2% crisaborole) ointment is a topical Phosphodiesterase-4 inhibitor approved for the treatment of mild to moderate atopic dermatitis (eczema) in patients of 2 years and older. The vehicle is a proprietary emollient that may have therapeutic value of its own. The only side-effect we have seen thus far has been burning on application to the skin. Some patients have decided to stop using it for this reason.
Chronic hives of unknown cause that have not responded to antihistamines
The medical name for this condition is chronic idiopathic urticaria. The approved drug is Xolair for patients of 12 years or older. It is a monoclonal antibody which blocks the effect of IgE. Xolair was first approved for moderate to severe persistent asthma in patients of 6 years or older. Because both of these conditions are more related to the field of Allergy and Immunology, we have decided to refer our patients to allergists for the injections which are usually administered in the office.
Pemphigus vulgaris (PV) is a rare, life-threatening autoimmune disease. Until this year, no drug had been approved to treat it although prednisone and assorted immunosuppressive drugs have been used for many years. The patients experience painful erosions and ulcers in the mouth that spreads to involve the skin with blisters. All of the lesions are very slow to heal. The cause of the blisters are antibodies in the circulation made by the patient’s own B-lymphocytes. We don’t know why this happens, but we now know how to stop it.
Rituxan is a biologic monoclonal antibody which targets the CD20 antigen on B-cells. A recent study done in Europe showed that patients treated with Rituxan + Prednisone were 3 time more likely to go into remission than those who received prednisone alone.
Rituxan was approved this year for PV. We will also probably prescribe it for a less common variant called Pemphigus foliaceous (PF). Rituxan was previously approved for severe rheumatoid arthritis and certain types of lymphoma and leukemia. It is dosed infrequently by intravenous infusion. For this reason, we have preferred to evaluate and diagnose such patients and then refer them to our local oncology centers with a prescription for the infusions. This system has been working out well, and the oncologists have been referring the patients back for our follow-up care.
You might ask, do we have enough treatments for psoriasis now? I think so. All of the treatments are temporarily remittive, that is, either partially or completely clear the skin. But when the medicine is stopped, the skin disease will gradually recur back to its original state, or possibly worse. Therefore, the next step in the investigation for psoriasis treatment should focus on curing the disease. I think we are very close to that now.
How about where we don’t have enough treatments or any at all? There are plenty of skin diseases that qualify. Some common ones are Alopecia Areata and Vitiligo. JAK inhibitors like Xeljanz have been shown to grow back hair and pigment, but a safer more practical approach would be to develop these drugs in a topical form.
We will need other CD20 monoclonal antibodies for pemphigus when patients have infusion reactions or develop allergies to Rituxan and for patients who do not have a good response.
We need treatments for Bullous Pemphigoid and Cicatricial Pemphigoid, autoimmune diseases similar to PV but not as severe. However, they affect mainly elderly people who likely have other co-morbidities, and we are seeing many more cases as our population ages and lives longer. Right now, the treatments include mainly prednisone and immunosuppressives that are not well-tolerated by these patients.
Less well known diseases that lack definitive treatments are Oral Lichen Planus, Pityriasis Rubra Pilaris, Granuloma Annulare, Necrobiosis Lipoidica, Pyodrma gangrenosum, Lupus of the skin, and Cutaneous T-Cell Lymphoma.
Pharmaceutical companies: Are you listening? There’s still a lot work to do.