Healthcare Provider Administration of Biologics for Patients with Plaque Psoriasis: Literature Review and Clinical Considerations

J Clin Aestet Dermatol 2023;16(12 Suppl 2):S20–S25

by Matthew Brunner, MHS, PA-C, DFAAPA; Keri Holyoak, MPH, MSHS, PA-C; and Douglas DiRuggiero, DMSc, MHS, PA-C

Mr. Brunner is with the Elevate-Derm Conference and Dermatology and Skin Surgery Center P.C. in Stockbridge, Georgia. Ms. Holyoak is with the Dermatology Center of Salt Lake in Midvale, Utah. Dr. DiRuggiero is with the Skin Cancer and Cosmetic Dermatology Center in Rome, Georgia.

FUNDING: Funding was provided by Sun Pharma.

DISCLOSURES: Mr. Brunner currently has a financial relationship and/or commercial interest(s) that may have a direct interest in this activity with the following entities: AbbVie, Amgen, Arcutis Biotherapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Dermavant Sciences, InCyte, Janssen, LEO Pharma, Lilly, Novartis, Ortho Dermatologics, Pfizer, Sanofi, Sun Pharma, and UCB. Ms. Holyoak currently has a financial relationship and/or commercial interest(s) that may have a direct interest in this activity with the following entities: Castle Biosciences, Dermavant Sciences, Galderma, InCyte, LEO Pharma, Pfizer, Sanofi, and Regeneron Pharmaceuticals. Dr. DiRuggiero serves as a speaker and is an advisory board member for Amgen, AbbVie, Arcutis Biotherapeutics, Bristol Myers Squibb, EPI Health, InCyte, Janssen, Lilly, Novartis, Sanofi, Regeneron Pharmaceuticals, and UCB.

ABSTRACT: Objective. Plaque psoriasis is a chronic, inflammatory, immune-mediated skin disease. Biologic therapies markedly improve skin disease severity and health-related quality of life for patients with moderate-to-severe plaque psoriasis. All but two of the biologics approved in the United States for moderate-to-severe plaque psoriasis may be self-administered by adult patients via subcutaneous injection. This review discusses rationales for choosing healthcare provider (HCP) administration over self-administration of biologics for patients with plaque psoriasis, including treatment adherence, patient preference, and practical considerations. 

Methods. PubMed was searched for “psoriasisAND biologic AND administration AND (office OR provider OR profession).”  The most relevant results and additional papers identified from the references were included in the review. 

Results. Although many patients prefer self-administration, others may benefit from HCP administration. Key considerations in the choice between HCP vs. self-administration of biologics for plaque psoriasis treatment include adherence, patient preferences, and practical concerns. Patient characteristics that may make HCP administration of biologic therapies for treatment of plaque psoriasis preferable to at-home self-administration are discussed. 

Limitations. There are few published studies specific to HCP administration of biologics for treatment of psoriasis. 

Conclusion. Administration of biologics by an HCP may improve treatment adherence and clinical outcomes compared to self-administration in selected patients with plaque psoriasis.

Keywords: Adherence, HCP administration of injectable biologics, plaque psoriasis, self-administration of injectable biologics

Targeted therapies, such as biologics, markedly improve disease severity and health-related quality of life for patients with moderate-to-severe plaque psoriasis.^1,2 Home-based therapies for dermatologic conditions are increasingly available due to their convenience and cost-effectiveness.³ All but two biologics approved in the United States (US) for moderate-to-severe plaque psoriasis may now be either self-administered by adult patients via subcutaneous (SC) injection or administered by a healthcare provider (HCP): infliximab and tildrakizumab both require HCP administration—infliximab by intravenous (IV) infusion and tildrakizumab by SC injection per the approved labeling (Table 1).^4–14 

Although many patients prefer self-administration, others may benefit from administration by their dermatology provider or at an alternative site of care, such as an infusion center. Therefore, patients and providers should engage in shared decision-making to inform treatment selection and optimize clinical outcomes.^15-17 Here, we review the evidence supporting HCP vs. self-administration of biologic therapies for plaque psoriasis and offer examples of patients for whom HCP administration might provide better experiences and outcomes compared with self-administration. 

Candidates for HCP Administration­—Patient Vignettes

Hypothetical Patient 1. A 35-year-old female patient presented with moderate-to-severe psoriasis involving the elbows, knees, and scalp (Psoriasis Area and Severity Index [PASI] score: 14). She was started on treatment with a tumor necrosis factor (TNF) inhibitor self-administered via SC injection. After months of therapy, the patient discontinued treatment despite initial improvement, reporting that she became tired of self-administering injections and experienced difficulty receiving pharmacy shipments due to work travel. She asked about alternatives to storing and injecting biologic therapies at home. The patient’s health insurance plan provided limited pharmacy benefits.

Hypothetical Patient 2. A 76-year-old male patient presented with moderate-to-severe psoriasis involving the scalp, trunk, and elbows (PASI score: 15). When counseled regarding potential treatment choices, he described his fear of needles and difficulty with manipulating syringes for self-injection of past medications. The patient also admitted to occasionally forgetting to administer shots of previous medications. The patient was widowed and living alone, reporting there was no one available at home to help him with injections. He described experiencing mild injection site reactions with his previous medications and expressed concern that more severe adverse reactions might occur when self-injecting at home. The patient was insured under Medicare Part B, but not Part D.

Advantages and limitations of Self-administration

The availability of different administration methods of biologics gives patients with psoriasis treatment options for their individual comfort levels, convenience, and insurance requirements.^{18, 19} Higher adherence and longer drug survival have been reported with HCP vs. at-home administration of psoriasis treatments; this may have been due to increased awareness (based on missed appointments) and the opportunity for the HCP to intervene.^{20, 21} Enhancing the patient-HCP relationship through frequent in-person contact may also improve adherence by increasing patient accountability.²² However, self-administration may be beneficial when office visits are limited. In an analysis of claims data during the COVID-19 pandemic, incidence of 14-day gaps in treatment increased by 55.1 percent (P<0.01) for patients using HCP-administered biologics for psoriasis, with no similar decrease in adherence for patients using biologics dispensed by pharmacies.²³

Poor patient experiences and problems with self-injection may decrease patient adherence and treatment efficacy.^24–26 Specific challenges for self-injection include needle phobia, fear and anxiety, concerns about injection site reactions, and limited visual acuity and hand dexterity.^24–27 Patients not provided with appropriate training for self-injection may rely on the product’s instructions for use and turn to a trial-and-error approach to self-administer their medication, which can result in habitualizing self-injection errors.²⁶ Even patients who receive training can make errors, and the dosing intervals of biologics (Table 1) mean that a single injection error could decrease efficacy for several weeks.²⁸

As self-administration of biologic therapy has both benefits and limitations, the main considerations when choosing between HCP vs. at-home administration are risk for poor adherence to treatment, patient preference, and practical considerations.

Risk for poor adherence to treatment

Continuity in treatment of patients with moderate-to-severe plaque psoriasis improves disease control and quality of life, compared to infrequent retreatment as needed.^{29, 30} However, treatment interruption is a concern in real-world use. A systematic review and meta-analysis of observational studies (2006–2020) reported mean adherence (5 studies) and persistence (46 studies) to 65 percent or less among adult patients with psoriasis being treated with biologics.³¹ Treatment discontinuation or switching may ultimately increase healthcare utilization and medical costs.^{32, 33} Among patients with moderate-to-severe psoriasis in two large US claims databases, adjusted mean total all-cause healthcare cost was lower for patients who discontinued versus those who remained on their index biologic (mean difference [95% confidence interval (CI)]: -$18,611 [-$20,254, -$17,025]) based on reduced prescription costs (-$20,486 [-$21,319, -$19,636]), but discontinuers had higher mean medical cost (including emergency department, inpatient, and outpatient costs) (mean difference [95% CI], $3,729 [$1,970, $5,527]).³² 

Factors associated with discontinuation of psoriasis treatment include lack of efficacy, adverse events (AEs) or other safety concerns, inconvenience, delayed refills, and cost.^15,16 Reluctance to self-inject may also contribute to discontinuation.²⁶ In the US Medicare population, lower adherence and higher discontinuation rates are observed for both younger (<65 years) and older (>75 years) patients, female patients, and patients ineligible for low-income subsidies.²⁰ Intentional nonadherence is more often associated with patients’ concerns about their medications, whereas unintentional nonadherence is more strongly associated with patients’ weaker medication-taking routines or habit strength.³⁴

Disease severity also affects treatment adherence. In a retrospective claims database analysis of patients with psoriasis being treated with biologics, treatment adherence and persistence decreased with increasing disease severity.¹ Greater mean adherence was observed in patients with mild (medication possession ratio [MPR], 77.3%; proportion of days covered [PDC], 73.0%) vs. moderate (MPR, 72.0%; PDC, 67.4%) or severe (MPR, 64.6%; PDC, 58.9%) disease.¹ Persistence to biologics also decreased with increasing disease severity (mean [standard deviation (SD)]: mild, 310.8 [92.6] days; moderate, 291.5 [106.7] days; severe, 262.7 [128.8] days).¹ 

Overall drug survival (a real-world measure of the time to drug discontinuation) was comparable among older (≥65 years) and younger (<65 years) patients with psoriasis in two studies.^35,36 However, in one of those studies, five-year drug survival among patients who discontinued due to ineffectiveness was lower in older (44.5%) vs. younger patients (60.5%).³⁶ Concomitant arthritis has also been associated with risk of discontinuing biologic treatment in patients aged 65 years or older.³⁵ Patients younger than 65 years of age who are female, obese, and/or biologic-experienced have poorer drug survival relative to patients without these characteristics.³⁵ Reasons for lack of adherence and persistence to biologic treatment in a literature review across chronic inflammatory diseases included forgetfulness, fear of self-injection, and reduced hand dexterity.³⁷ 

Patient preference

Patients with psoriasis have individual preferences for administration route, treatment setting, and dosing frequency and may prefer IV infusion, SC injection by an HCP, or at-home SC self-injection.³⁸ In a systematic review of studies on patient preferences for the treatment of chronic immune disorders, the majority of patients preferred self-administration of SC injections over HCP administration of IV infusions.¹⁷ Patients who preferred IV infusions often appreciated the associated lower dosing frequency, compared to that of SC administration; patients with psoriasis generally preferred treatments with less frequent injections.^17,18,39

Another reason given by patients who preferred IV infusion over self-administration of SC injections was the presence of medical staff during treatment.^17,18,40,41 Patients (and payers) may desire to have an HCP present during administration to monitor for AEs.^18,41,42 The importance of HCP supervision for safety of biologic treatment has been noted in other inflammatory diseases, by both patients and providers. A virtual community meeting of HCPs and patient organization representatives reported that many patients with inflammatory bowel disease felt safer with treatment administration in the hospital setting, where treatment is provided by professionals.⁴³ In view of the potential for AEs associated with biologic therapy, the American College of Rheumatology position statement encourages administration of biologics to patients with rheumatoid arthritis at a treatment center with specially trained practitioners instead of at-home treatment.⁴⁴ Finally, patients may value the opportunity to consult with HCPs and to socialize and share experiences with other patients during treatment visits.^18,42 

Patient preferences may also be driven by negative perceptions, including dislike or fear, of SC self-injection.^17,18,43 Patients may perceive SC injections as uncomfortable or painful.¹⁸ Some may worry about incorrect self-administration, including their ability to properly select an appropriate injection site or inject.^18,28,39,45 Others may have concerns or difficulty with remembering dosing schedules.^18,46 Reduced hand dexterity may complicate self-injection.⁴⁵ In the authors’ clinical experience, some patients report consistent difficulty with injecting the entire dose due to lack of dexterity. Patients may also have concerns about the logistics of SC self-injection, including availability to receive medication packages and properly disposing of used needles, as well as needing to carry equipment and/or medication with them.^18,28

Practical considerations

All biologic therapies approved for the treatment of plaque psoriasis may be administered by an HCP, including therapies that are also approved for self-administration, offering flexibility to patients and providers.^4–14,47 One consideration when choosing among biologic therapies for plaque psoriasis is dosing frequency (Table 1), as biologics with longer (i.e., 12-week) dosing intervals may be more convenient for HCP administration relative to those dosed every two or four weeks.^6–9

Proper storage and handling of biologic medicines is important to maintain their stability and effectiveness. However, in one study, 82.7 percent of patients receiving biologic therapies for inflammatory rheumatic diseases did not maintain their medications under the recommended temperature conditions (2–8 °C), based on temperatures measured within their home refrigerators; in another study, only 6.7 percent of patients stored all of their packages of biologics within the recommended temperature range, when actual storage temperatures were recorded over time.^48,49 Patients may also experience difficulties with shipments being left outdoors for extended periods. Furthermore, patients may have concerns about storing their medications while traveling.⁴⁸ 

Treatment setting and the financial complications of direct versus indirect drug supply may affect the availability of healthcare insurance coverage and reimbursement for various therapies.⁴⁷ Self-administered drugs generally are not covered by Medicare Part B medical insurance but may be covered by the Medicare Part D drug plan.^19,47 Medicare patients without Part D coverage may utilize certain agents in the infusion center or office setting because these will be covered by Part B. Treatments labeled for self-injection may require payment authorization for HCP administration, which can make those labeled for HCP administration only, such as infliximab and tildrakizumab, more accessible.^4,5

Conclusion

Key considerations for choosing between HCP administration and self-administration include treatment adherence, patient preferences, and practical matters. From our review of these considerations, we propose patient characteristics that might make HCP administration of biologic therapies for treatment of plaque psoriasis preferable to at-home self-administration (Table 2). Based on these characteristics, both hypothetical patients in the opening vignettes would, in the authors’ opinions, be good candidates for HCP administration of a biologic in-office or in an alternative care setting: Patient 1 due to personal preference and convenience concerns and Patient 2 due to personal preference, limited dexterity, adherence problems, and insurance coverage.

Identifying patients who may benefit from in-office administration of biologics may improve adherence and persistence, which could ultimately reduce psoriasis-related healthcare resource utilization.^21,32 Additionally, incorporating patient preferences, including those regarding HCP administration versus self-administration, into shared decision-making may increase patient satisfaction with treatment and encourage adherence, thus improviong clinical outcomes for patients with plaque psoriasis.^15–17,50 

Acknowledgments

Medical writing support was provided by Elisabetta Lauretti, PhD, and Somdutta Mukherjee, PhD, of AlphaBioCom, a Red Nucleus company, and funded by Sun Pharma.

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