Numerous options are currently available for the treatment of psoriatic arthritis, ranging from simple nonsteroidal anti-inflammatory drugs (NSAIDs) to conventional disease-modifying antirheumatic drugs (DMARDs) and to new targeted biologics and small molecules. The first steps in developing a treatment plan for an individual patient is to identify the patient's goals in therapy and determine the severity of disease.
Individualize the Treatment
"The first thing we do is really try to get a sense of who the patient is, what their disease and their experience of it is like, and what they want to get out of treatment," said Rebecca Haberman, MD, of NYU Langone Health in New York City.
Psoriatic arthritis is a very heterogeneous disease, with some patients having more joint involvement, others having more skin and nail involvement, and for others, the disease is in the spine.
"We ask when skin and joint symptoms first began, how the symptoms affected the patient over time, and if any previous treatments have helped. We have a lot of options right now, injectable and oral, with some being better for different aspects of the disease, so we want an idea of what is the most problematic to them," Haberman told 乌鸦传媒.
The initial evaluation of the patient involves determining the extent of illness both from a skin perspective and from an arthritic perspective, explained Dee Dee Wu, MD, of the Hospital for Special Surgery in New York City. "We need to address both, ideally with a single medication," she said.
Initial treatment, especially for patients with milder disease, can involve an oral DMARD such as methotrexate. Other oral options that can address both the skin and arthritic symptoms include apremilast (Otezla) and tofacitinib (Xeljanz), Wu noted. But for those with severe skin problems or arthritis, a biologic such as a tumor necrosis factor (TNF) inhibitor may be needed. In addition, NSAIDs can be used to help with symptom control at all levels of treatment.
Another important concern in treatment choice is the presence of comorbidities. "For example, for patients with a lot of gastrointestinal problems, you might want to avoid apremilast because that can cause GI upset," said Haberman.
Patients also could have conditions such as cancer or congestive heart failure and could have contraindications to certain medications, said Wu. "There really is no set algorithm in terms of deciding on treatment because it's individualized to the patients' symptoms and their other medical conditions. You don't want to overtreat but you don't want to undertreat either, so that's where the finesse come in," she said.
And there still is an element of trial and error in treatment choices.
"It's great that we have all these options, but one thing we don't know right now is which medication will be best for an individual patient. This is something that is being studied and one of the goals of the field is to have more precision treatment," said Haberman.
"If one medication doesn't work we can try another one with a different mechanism of action. So one thing we always tell patients is if the first medication doesn't get us to where we want to go, don't get discouraged, because we can treat in different ways with different mechanisms," she added.
Options for Moderate to Severe Disease
The TNF inhibitors such as etanercept (Enbrel) and adalimumab (Humira) have been available for the treatment of more resistant psoriatic arthritis since the 2000s, and have shown effectiveness for multiple disease domains, including psoriasis, nail disease, and peripheral and axial arthritis, as well as enthesitis and dactylitis.
But several more targeted treatments have become available in recent years, as greater understanding of the pathogenesis of psoriatic arthritis has led to refinements in treatment.
Research revealing the role of various cytokines such as interleukin (IL)-17 and IL-23 allowed the development of agents such as secukinumab (Cosentyx), ixekizumab (Taltz), and guselkumab (Tremfya), and investigations into the Janus kinase (JAK)-signal transducer and activator of transcription pathway permitted the development of oral agents such as tofacitinib.
In 2016, the IL-17A inhibitor secukinumab was approved for use in psoriatic arthritis following the publication of the and 2 trials, and the benefits of treatment with this agent , regardless of whether patients had previous exposure to TNF inhibitors and were using concomitant methotrexate.
Another IL-17A inhibitor, ixekizumab, was approved in 2017 after efficacy was demonstrated in the . As reported in a at the American College of Rheumatology (ACR) 2020 virtual meeting, fewer serious adverse events were observed among patients receiving ixekizumab in a 52-week open-label trial than among those given adalimumab (3.2% vs 7.1%).
The newest biologic for psoriatic arthritis is guselkumab (Tremfya), which is a monoclonal antibody targeting the p19 subunit of IL-23 that was approved in July 2020. In the pivotal DISCOVER 1 and 2 trials, 20% improvement on ACR criteria (ACR20) responses were seen at rates of 52% and 64%, respectively, among patients randomized to guselkumab compared with 22% and 33% for those given placebo.
"The results were consistent with what we have come to expect from the best-performing drugs in psoriatic arthritis," the lead author of DISCOVER 2, Philip Mease, MD, of the University of Washington in Seattle, told 乌鸦传媒.
In another presentation at the ACR virtual meeting, for guselkumab were reported by Iain B. McInnes, MD, PhD, director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow in Scotland. After 1 year of treatment, ACR20 responses were seen in 70.6% of patients given 100 mg every 4 weeks and in 74.6% of those given the treatment every 8 weeks. Benefits also were seen for dactylitis and enthesitis and on the Health Assessment Questionnaire Disability Index.
Even more targets for the treatment of psoriatic arthritis are under development, with several presentations at the ACR virtual meeting showing promise for another IL-23 agent, a tyrosine kinase 2 inhibitor, and a new JAK inhibitor. These will be reviewed in the next part of this Clinical Challenges series.