The newest frontier for biologics and psoriasis may be adherence

By Warren R. Heymann, MD
June 19, 2019
Vol. 1, No. 15

My first job as an attending dermatologist was heading the psoriasis day care center at the Albert Einstein College of Medicine in 1983. The challenges of treating severe psoriasis with the Goeckerman regimen, PUVA, methotrexate, etc. made the concept of a PASI 100 virtually unfathomable. Thirty-six years later, while not the norm for all patients, it is achievable for many. Patients who used to require intensive visits, now smile, with relatively few adverse reactions, get their TB status checked, and visit every six months. I am in awe of these advances. 

Adherence has always been an important issue for psoriatic patients. Regarding topical therapy, a survey of 79 Portuguese patients with psoriasis suggested that a simple dosing regimen of an agent with good moisturizing properties, in a vehicle formulated to provide fast absorption, was essential. Other important attributes to the topical product which promote adherence are leaving a minimum residue, not staining clothing, and allowing the patient to get dressed shortly after applying the medication. (1)

Assuming there are no contraindications to using biologics for psoriatic patients (chronic infections such as tuberculosis, hepatitis B, HIV; concurrent malignancies, notably lymphoproliferative disorders; simultaneous use of other immunosuppressive agents, etc.), there are still hurdles to get patients started on biologics. Prohibitive costs and insurance authorization lead the list. Just as important, however, is overcoming the fear factor. “Dr. Heymann, my next door neighbor’s aunt’s son-in-law’s cousin’s college roommate got an infection from it — I don’t want to use them!” No matter how hard I try to put this in perspective — “You have a greater risk dying in a car accident coming to this appointment!” — I have several patients who absolutely refuse to use biologics; the perceived risk, despite published safety studies and my regaling success stories, is just too great for them.

For patients on biologics, are there problems with adherence?

According to Murage et al, “Adherence and persistence to biologic therapy reflects various factors such as treatment effectiveness, drug safety and adverse event profile, tolerability, quality of life, and cost.” In their cohort of 2130 biologic-treated patients (IQVIA Pharmetrics Plus adjudicated claims database linked to Modernizing Medicine Data Services), 24% of all biologic-treated patients discontinued biologic therapy during the one-year follow-up period. Overall adherence to biologics was < 75% — this is considered inadequate based on the 80% threshold that defines adherence in the Medication Possession Ratio (MPR). There appeared to be a trend of decreasing adherence with increasing disease severity, suggesting that the biologic treatment regimens used in this study (etanercept, adalimumab, infliximab, ustekinumab, and secukinumab) were not providing an optimal treatment response. (2)

How does adherence for biologics compare to older treatments such as methotrexate or acitretin?

Dommasch et al conducted a retrospective, comparative cohort study using a large U.S. health insurance claims database (United Healthcare) including psoriasis patients who were new users of acitretin, adalimumab, etanercept, methotrexate, or ustekinumab. Adherence was measured by using proportion of days covered dichotomized as adherent (≥0.80) or nonadherent (<0.80). Odds ratios (ORs) and 95% confidence intervals (CIs) comparing adherence to each exposure (acitretin, adalimumab, etanercept, or ustekinumab) to the referent (methotrexate) were estimated via logistic regression, with pairwise 1:1 propensity score matching to adjust for potential confounders. In total, 22,742 patients were new users of systemic medications. Among these patients, adherence to adalimumab (OR 2.24); etanercept (OR 1.77); and ustekinumab (OR 2.54) was greater and acitretin (OR 0.57) lower compared with methotrexate.

A limitation of the study was that the authors were unable to evaluate reasons for discontinuation. Of note is that there was a higher adherence rate for ustekinumab compared to other biologics (I presume that every third month dosing may be a factor). I was surprised to learn that men were more likely to be adherent to every systemic medication, except for methotrexate, which was adhered to equally in men and women. The authors concluded that there is greater adherence to biologics than methotrexate in new users, and suggesting further research to understand why there is overall low adherence to systemic medications for psoriasis. (3)

The finding about compliance in men versus women surprised me. In a study of 29.5 million adults (13.5 million men and 16 million women) analyzing pharmacy benefits, defining adherence as MPR > 80%, for all clinical metrics evaluated, women were less likely than men to be adherent in their chronic use of medications, and they were less likely to receive the medication treatment and monitoring recommended by clinical guidelines. (4) Dommasch et al noted that the cause for the gender discrepancy is unknown, although psychosocial factors, differences in patient-provider interactions, and the caregiver status of women may play a role. (3)

Current biologics for psoriasis include anti-TNF agents and monoclonal antibodies directed against IL-12, IL-23, IL-17A, and the IL-17 receptor. Given the plethora of effective drugs, with more in the pipeline, perhaps renewed emphasis on adherence is even more important than developing a new drug. Focusing on those factors that may influence adherence such as disease severity, comorbidities, costs, and awareness of drug effectiveness, safety, and tolerability (5) should be paramount in improving adherence to these outstanding medications. 

Point to remember: There are many factors that determine adherence to biologics in patients with psoriasis — all of them need attention to ensure optimal care. 

Our expert’s commentary

Steven R. Feldman, MD, PhD
Professor of Dermatology
Wake Forest School of Medicine
Adjunct Professor of Dermatology
University of South Denmark

This outstanding commentary provides a synthesis of a tremendous amount of information on one of the most critical factors — adherence — that determines our patients’ outcomes. Once we’ve made the right diagnosis and prescribed an appropriate treatment, the degree to which the patient takes the medication may account for much of, if not most of, the variation in response to treatment. If our goal is to get our patients well, attending to adherence issues and developing the skills required to do so may be good uses of our time.

1. Vasconcelos V, et al. Patient preferences for attributes of topical anti-psoriatic medicines. J Dermatolog Treat 2018; Nov 23: 1-19 [Epub ahead of print].
2. Murage MJ, et al. Treatment patterns, adherence, and persistence among psoriasis patients treated with biologics in a real-world setting, overall and by disease severity. J Dermatolog Treat 2018; Jul 23: 1-9 [Epub ahead of print].
3. Dommasch ED, et al. Drug utilization patterns and adherence in patients on systemic medications for the treatment of psoriasis: A retrospective, comparative cohort study. J Am Acad Dermatol 2018; 79: 1061-1068.
4. Manteuffel M, et al. Influence of patient sex and gender on medication use, adherence, and prescribing alignment with guidelines. J Women’s Health 2014; 23: 112-119. 
5. Murage MJ, et al. Medication adherence and persistence in patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis: A systematic literature review. Patient Prefer Adherence 208; 12: 1483-1503. 

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