What Is the Future of Psoriatic Arthritis Treatment?

PSORIATIC ARTHRITIS (PSA) is a chronic inflammatory disease characterized by joint pain, stiffness, and swelling and clinically presents as axial or peripheral arthritis, dactylitis, and nail or skin lesions. Usually PsA occurs after the development of psoriasis. However, in a small number of patients, joint problems begin before psoriasis appears.¹

More than 8 million Americans live with psoriasis, and PsA affects between 15% and 30% of those individuals.² The disease also affects men and women almost equally, with a peak onset age between 40 and 50 years, although it can begin at any time.^1,3 A hereditary link also appears evident, as individuals who have a first-degree relative with the condition have a 40% greater chance of developing the disease.⁴

Effective and timely treatment is important in PsA because the earlier it is diagnosed, the sooner treatment can begin, thus slowing down permanent joint and tissue damage and the progression of disability.¹ However, diagnosis is often delayed because of the generality of symptoms, and study results show that just 30% of patients receive a proper diagnosis within the first 6 months of symptom onset.^5,6

Although the number of drugs for PsA has increased over the past decade, half of treated patients still do not achieve optimal outcomes, and little guidance exists to help practitioners with medication choice. Physicians make their decisions based on the clinical disease domain affected, cost, and provider familiarity.⁷

Considerations and Goals of Therapy

No cure for PsA exists, so the goals of treatment are to slow disease progression, improve quality of life, lessen pain, and preserve range of motion. With variable presentation and 5 subtypes of disease, practitioners must assess the clinical presentations and locations affected and choose therapy accordingly.^6,7

Therapeutic treatment is usually focused on a particular goal, with minimal disease activity (MDA) criteria recommended as the treatment target in patients with PsA. Evidence shows that patients who meet those criteria have better quality of life, less joint damage, and more functional ability.⁷ Practitioners also need to consider comorbidities because patients suffering from PsA are more likely to have cardiovascular disease, metabolic syndrome, depression, and diabetes.^1,4

Treatment Selection and Strategies

In most patients with PsA, pharmacological treatment consists of a trial-and-error approach, beginning with corticosteroids and nonsteroidal anti-inflammatory drugs to manage symptoms. Physicians often use conventional synthetic disease-modifying antirheumatic drugs (DMARDs), followed by biological DMARDs if a patient does not adequately respond.^1,2 However, the American College of Rheumatology (ACR) and the National Psoriasis Foundation have challenged this historical approach, instead recommending biological DMARDs as first-line therapy.^2,3,7,8

Biological therapy has 5 mechanisms, with tumor necrosis factor (TNF) inhibitors the most established. Patients often receive these as first-line therapy because of more robust outcome data, physician familiarity, and lower costs due to TNF biosimilars. Interleukin (IL-17A, IL-12, and IL-23) inhibitors tar get disease-specific cytokines. Oral small molecules include Janus kinase inhibitors that block the downstream signal of multiple cytokine receptors and a PDE4 inhibitor that blocks the degradation of cyclic adenosine monophosphate in immune cells, thus inhibiting an inflammatory response.^7,9

A preferred hierarchy of drug selection has not been established, and because of the clinical heterogeneity of PsA, large studies need to evaluate the different clinical domains of the diseases. To date, only 1 large head-to-head study has compared biologics for PsA. In that study, Mease et al compared the IL-7 inhibitor ixekizumab with adalimumab, and results showed the superiority of ixekizumab in the primary outcome of patients achieving ACR50 criteria and 100% reduction in the Psoriasis Area and Severity Index.¹⁰ The study results also showed noninferiority to adalimumab.¹⁰

Physicians have no way to predict who will and will not respond to therapies, and because biological and targeted synthetic DMARD treatment usually lasts for 12 to 24 weeks, a longer period of suboptimal therapy may result.^2,3 These delays can also contribute to both negative outcomes and decreased quality of life.

Future Direction

The approach of using biologics in patients with PsA without an evidence-based stratification or personalization tool has led to more than 50% of patients not meeting their therapeutic target as defined by the MDA criteria. Some patients who have failed prior first-line biological therapy may have a response when they switch to a drug with a different mechanism of action, which may suggest that disease pathogenesis can differ among individuals.^7,11

In 2019, the first study addressing precision medicine in PsA was published. Miyagawa and colleagues conducted the trial and looked at evaluating baseline CD4 T-cell activation markers to select appropriate therapy for patients with PsA.¹² Even though the trial had limitations, the results were promising, and it was the first study to use baseline immunophenotyping when selecting therapy.^7,12

Personalized treatment selection has had success in other autoimmune disease states, such as rheumatoid arthritis. In the future, a combination of immunophenotyping and statistical analyses could assist in a targeted treatment approach that has the potential to maximize outcomes in patients with PsA without delay.⁷

What Pharmacists Should Know

Many effective DMARDs are available. However, patients respond differently and may not achieve optimal outcomes with their first choice of treatment, which contributes to delays and poorer long-term results. Practitioners should base treatment selection on clinical areas involved, comorbidities, and evidence. Many biologics also have specialty distribution pathways, which can present a challenge to patients who must navigate the system.

Although new treatment selections offer opportunities for therapy, they also present new challenges, and pharmacists must be knowledgeable about evidence-based studies that can help guide and individualize treatment for PsA.

Joanna Lewis, PharmD, MBA, has worked in a variety of practice settings, most recently as a coordinator at Duke University Hospital in Durham, North Carolina.

REFERENCES

• Liu JT, Yeh HM, Liu SY, Chen KT. Psoriatic arthritis: epidemiology, diagnosis, and treatment. World J Orthop. 2014;5(4):537-543. doi:10.5312/wjo.v5.i4.537
• Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis. National Institute for Health and Care Excellence. August 25, 2010. Accessed March 16, 2020. https://www.nice.org.uk/guidance/TA199/chapter/1-Guidance
• About psoriatic arthritis. National Psoriasis Foundation. Updated January 15, 2020. Accessed March 15, 2020. https://www.psoriasis.org/about-psoriatic-arthritis
• Ogdie A, Weiss P. The epidemiology of psoriatic arthritis. Rheum Dis Clin North Am. 2015;41(4):545-568. doi:10.1016/j.rdc.2015.07.001
• Haroon M, Gallagher P, FitzGerald O. Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis. Ann Rheum Dis. 2015;74(6):1045-1050. doi:10.1136/annrheumdis-2013-204858
• Mease PJ, Gladman DD, Papp KA, et al. Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol. 2013;69(5):729-735. doi:10.1016/j.jaad.2013.07.023
• Al-Mossawi H, Taams LS, Goodyear C, et al. Precision medicine in psoriatic arthritis: how should we select targeted therapies. Lancet Rheumatol. 2019;1(1):e66-e73. doi:10.1016/S2665-9913(19)30008-6
• Singh JA, Guyatt G, Ogdie A, et al. 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. J Psoriasis Psoriatic Arthritis. 4(1):31-58. doi:10.1177/2475530318812244
• Coates LC, Mease PJ, Gossec L, et al. Minimal disease activity among active psoriatic arthritis patients treated with secukinumab: 2-year results from a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase III study. Arthritis Care Res (Hoboken). 2018;70(10):1529-1535. doi:10.1002/acr.23537
• Mease PJ, van der Heijde D, Ritchlin CT, et al; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. doi:10.1136/annrheumdis-2016-209709
• Fagerli KM, Kearsley-Fleet L, Watson KD, et al. Long-term persistence of TNF-inhibitor treatment in patients with psoriatic arthritis. Data from the British Society for Rheumatology Biologics Register. RMD Open. 2018;4(1):e000596. doi:10.1136/rmdopen-2017-000596
• Miyagawa I, Nakayamada S, Nakano K, et al. Precision medicine using different biological DMARDs based on characteristic phenotypes of peripheral T helper cells in psoriatic arthritis. Rheumatology (Oxford). 2019;58(2):336-344. doi:10.1093/rheumatology/key069