New Biological Agents for Psoriatic Arthritis: A Monoclonal Antibody Primer

Background

Psoriatic arthritis (PsA) is a chronic inflammatory disease that primarily affects the musculoskeletal system. PsA is manifested from plaque psoriasis (PsO) and is associated with peripheral arthritis, dactylitis, enthesitis, and spondylitis.¹ Disease remission and symptom treatment may be achieved with both non-pharmacologic and pharmacologic modalities.

There are many pharmacologic treatment options available to help manage PsA, including NSAIDs, glucocorticoids, intraarticular glucocorticoid injections, and immunomodulatory therapies.¹ Most clinicians prescribe immunomodulating therapies, which are available in various formulations. A common class of therapies utilized are biological agents – or more specifically, monoclonal antibodies (mAbs) – which have evolved over the past decade, providing more approaches for treatment and allowing for drug targeting.

This overview aims to explain this group of therapies in the context of PsA.

Monoclonal Antibodies: How They Are Named

The cornerstone of today’s psoriatic arthritis biologic treatment is the continued development of mAbs. These immunoglobulins are exogenously produced from a single parent cell.² The nomenclature of these agents provides information on the drug target and type of originating cell.

The key elements of an mAb name are in this order:

• prefix
• infix (representing the target)
• infix (representing the sequence)
• suffix (-mab).³

The nomenclature is based on the United States Adopted Names program (USAN) and the international non-proprietary names (INNs) expert panel.^3,4 Figure 1 demonstrates this structure.

The infix may be further broken down into two subcategories:

• substem A
• substem B.

Substem A specifies the target of the antibody, such as interleukin or immune related target, while substem B specifies the sequence from which the antibody was derived, such as mouse or human.² For example, the substem A (-ki) indicates the drug targets the interleukin pathway and the substem B (-xi) means the drug was derived from chimeric cells (see Table I). The most commonly used suffix for monoclonal antibodies is (-mab). Monoclonal antibodies for the treatment of PsA primarily target the interleukin or immune system.

Specific mAbs for Managing Painful Psoriatic Arthritis

Monoclonal antibodies are desirable for the management of PsA given their unique ability to target specific inflammatory pathways in the immune system. These biologics can better regulate or reduce the immune related inflammatory responses that have been associated with PsA. The reduction in inflammation can prevent long-term joint damage and improve functionality. Other medications used to treat PsA, such as NSAIDs and glucocorticoids, do not target specific immune-related inflammatory pathways to prevent long-term joint damage.

Biologics such as mAbs are typically reserved for the treatment of moderate-to-severe PsA in patients who have not responded to other treatments.

There are two major mAb classes used in the management of psoriatic arthritis:

• tumor necrosis factor inhibitors (TNF-i)
• interleukin pathway inhibitors (IL-12/-23/-17i)

The American College of Rheumatology (ACR) 2018 guideline recommends the use of a TNF-i before considering an IL agent. It is unclear whether one class is more efficacious than the other, however, TNF-i tend to be preferred due to their longer time on the market and potentially lower cost.

TNF Inhibitors

TNF-i were first to appear on the market with the approval of infliximab (Remicade) in 1998. The first IL-12/23 emerged in 2009 with the approval of ustekinumab (Stelara). Today, there are several newly developed therapies with unique nomenclature as shown in Table II.

Interleukin Agents

Interleukin inhibitors (IL) have been a popular target in drug development for the management of both PsA and PsO as well, with five of these agents FDA approved since 2016:^6-10

• ixekizumab (Taltz)
• brodalumab (Siliq)
• guselkumab (Tremfya)
• tildrakizumab (Ilumya)
• risankizumab (Skyrizi).

These agents differ in dosing and mechanism of specific IL targets, shown in Table III. Regulatory approval of these agents has provided alternative treatment options for patients with complex disease progression.

Unfortunately, the accessibility of these agents to patients may be limited due to the burden of cost. As with many mAbs and newly approved drugs, generic substitutions are nearly nonexistent. Most of the agents have FDA approval for the treatment of PsO instead of PsA, however, maintenance treatment of PsO may provide PsA relief due to these cohabited disease states.

See also, evolving strategies for treating osteoarthritis.

In Summary

Understanding the naming of these new monoclonal antibodies may provide insight and guidance to providers on the desired target for treatment of psoriatic arthritis. TNF-i and IL agents may be beneficial for patients with moderate-to-severe disease who have not responded to other therapies. The use of these agents may reduce pain and improve disability through the prevention of long-term joint damage. When choosing an agent, clinician should refer to clinical practice guidelines and evidence-based literature to make the best choice for their patients.

The author would like to express gratitude to residency program director Lindsay B. Wells, PharmD, BCPS, and Jeffrey Fudin, PharmD, FCCP, FASHP, FFSMB, for their guidance, support, and feedback in developing this article.