Pearls to optimize safety, success with biologics

December 5, 2016

One dermatologist describes his considerations for choosing a biologic to treat a patient with moderate-to-severe psoriasis, baseline assessments, and follow-up approach.

In the experience of Jeffrey Sobell, M.D., treatment of moderate-to-severe plaque psoriasis with biologics has been extremely rewarding and has produced some of the happiest and most satisfied patients he sees. Optimizing safety and success, however, requires knowledge of the warnings and precautions pertaining to each agent, careful patient follow-up, and ongoing counseling.

Speaking at the Fall Clinical Dermatology Conference, Dr. Sobell discussed how he tailors his selection of a biologic agent to the individual’s medical history along with his approaches for treatment initiation and follow-up.

Dr. Sobell“There are now six biologics with an FDA-approved indication for treatment of moderate-to-severe psoriasis representing three different mechanistic categories. Maximizing safety is paramount for all treatment decisions, and while the available biologics share many attributes, there are some important differences in their safety profiles,” says Dr. Sobell, assistant professor of dermatology, Tufts University School of Medicine, Boston.

The biologics approved for the treatment of moderate-to-severe psoriasis include three tumor necrosis factor-α (TNF-α) antagonists - etanercept (Enbrel, Amgen), infliximab (Remicade, Janssen Biotech), and adalimumab (Humira, AbbVie); one interleukin (IL)-12/23 antagonist -ustekinumab (Stelara, Janssen Biotech), and two IL-17A antagonists - ixekizumab (Taltz, Eli Lilly) and secukinumab (Cosentyx, Novartis).

Considerations for biologic use

Dr. Sobell says that no biologic should be used in a patient with an active serious infection. In addition, screening for tuberculosis (TB) and viral hepatitis is mandatory.

“TNF-α antagonists should be used with caution in anyone with a history of hepatitis B infection because the virus can be reactivated, but these biologics are probably the systemic treatment of choice in anyone with concomitant hepatitis C infection,” he explains.

Dr. Sobell also considers the use of any biologic very carefully in patients with a history of malignancy, although a warning about increased risk of malignancy appears only in the labeling for the TNF-α antagonists and the IL-12/23 inhibitor.

“We know that the TNF-α antagonists are associated with an increased risk of squamous cell carcinoma of the skin, but there is not solid evidence to guide treatment decisions for patients with a history of any malignancy. My decision in patients with a history of a solid tumor is individualized based on a discussion with the patient and the oncologist,” Dr. Sobell says.

In addition, based on warnings and precautions in the product information, he does not use TNF-α antagonists in anyone with a demyelinating disease (eg., multiple sclerosis), moderate-to-severe congestive heart failure, or chronic carriers of hepatitis B. And, Dr. Sobell says he tends to avoid etanercept in patients who are obese because of evidence that individuals weighing more than 200 pounds are less likely to achieve a good response.

NEXT: Considerations with common comorbidites

 

 

Considerations with common comorbidities

The individualized treatment decision also takes into account diseases that are seen more frequently in patients with psoriasis, and those include inflammatory bowel disease (IBD), psoriatic arthritis, and cardiovascular disease.

Because infliximab, adalimumab, and ustekinumab have indications for IBD, they are preferred for patients with that history, whereas IL-17A antagonists are generally less favored considering rare reports linking them with IBD development or exacerbation.

Dr. Sobell notes that all of the biologics except ixekizumab are indicated for treatment of psoriatic arthritis. Based on available experience and assuming absence of any contraindications, his preference for treating patients with comorbid psoriatic arthritis is to use a TNF-α antagonist.

“The IL-17A drugs have also demonstrated solid success treating psoriatic arthritis, and I expect ixekizumab will be approved for that indication soon,” Dr. Sobell says.
“Reported results are least robust for ustekinumab, and that is consistent with my personal experience.”

Dr. Sobell also favors a TNF-α antagonist for patients with coronary artery disease. That preference takes into account a retrospective analysis of psoriasis patients showing a 48% reduction in myocardial infarction risk with use of a TNF-α antagonists compared with topical agents.

“Based on a shared inflammatory pathway, psoriasis itself is a risk factor for cardiovascular disease, and ongoing studies are investigating whether TNF-α antagonists have cardioprotective benefits,” Dr. Sobell says.
Getting started

In order to decide candidacy for biologic treatment and to obtain baseline information for judging treatment response, patients are asked about severity of their symptoms, particularly itch but also pain. They are also assessed for body surface area (BSA) and anatomic areas of involvement, and their disease severity is rated using the 5-point Physicians Global Assessment (PGA) scale.

“Location of disease is extremely important and not just area of involvement. There is a lower threshold for using a biologic agent for psoriasis affecting the hands, feet, genital area, or scalp,” Dr. Sobell says.

The initial laboratory work-up includes a complete blood count, full chemistry panel with liver function tests and screens for TB and hepatitis as well as pregnancy if appropriate. Dr. Sobell also obtains a geographic-directed history for deep fungal infection and noted that no patient on a biologic should be given a live vaccine.  

Prior to treatment initiation, patients also receive extensive face-to-face education supplemented with brochures and information about online resources, particularly from the manufacturers and the National Psoriasis Foundation.

“The manufacturers are also a good resource for providing staff with guidance on obtaining prior authorization, which can be particularly frustrating,” Dr. Sobell says, adding that the process becomes easier over time and seems to have improved as more treatments have become available.

Patients are evaluated for response at 12 weeks, taking into account that the peak benefit with some biologics may not be reached for another four to 12 weeks. The decision to continue is based on the physician’s and patient’s satisfaction with the improvement achieved, although for Medicare patients, PQRS guidelines suggest a PGA score of clear or almost clear or BSA <3%.

During the first year after treatment initiation, Dr. Sobell sees patients every three months and then transitions to a semi-annual follow-up schedule.
“In addition to monitoring efficacy and safety by conducting a complete review of systems, I also continue to stress adherence to the injection protocol at each visit and make sure patients are being followed by their primary care physician,” he said.

A full skin examination is done at least once a year, and the initial laboratory tests as well as a TB screen are also repeated annually.

Disclosure: Dr. Sobell is an investigator, consultant and speaker for a number of companies that market biologics for inflammatory skin diseases.