With the rapidly increasing array of treatments for psoriatic arthritis (PsA), factors that can help in the choice of medication include the specific disease phenotype and comorbidities. “We look at the person as a whole,” said M. Elaine Husni, MD, MPH, vice chair of Rheumatology and director of the Arthritis and Musculoskeletal Center of the Cleveland Clinic.
One component in the choice of treatment involves recognizing the domains of disease. “Finding the right treatment can be framed by the phenotype — the flavor of disease if you will — with six main clinical domains: peripheral arthritis, axial disease, enthesitis, dactylitis, skin, and nails,” said Joseph F. Merola, MD, of Brigham and Women’s Hospital in Boston, speaking in a webcast sponsored by the Autoimmune Learning Network.
Initially the patient can be categorized as having mild, moderate, or severe disease, Husni explained. “For the patient with mild disease, we would use more of the oral and topical therapies. As the disease becomes more moderate to severe, or the patient doesn’t respond to initial therapies, we start thinking about the newer medications like the biologics or targeted synthetics,” depending on the disease phenotype, she said.
“For instance, if the patient has more skin involvement, I might choose an interleukin [IL]-17 inhibitor. Or if they have more joint involvement and less skin, I might use a tumor necrosis factor [TNF] inhibitor,” she said.
In addition, “a patient with enthesitis might respond better to a biologic rather than a conventional agent such as methotrexate, while if they have more prominent axial disease rather than peripheral arthritis, we would use a TNF inhibitor or IL-17 blocker,” she said.
“We also have to consider the comorbidities, and the list of comorbidities is long,” Merola said. These include uveitis, renal disease, hepatosteatosis, chronic obstructive pulmonary disease, sleep apnea, depression, metabolic syndrome, diabetes, dyslipidemia, peripheral vascular disease, gout, myocardial infarction, and stroke. “It takes a team of providers to manage PsA, including dermatologists and rheumatologists,” he added.
In 2016, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) published a practice guideline in Arthritis & Rheumatology with treatment recommendations.
The ultimate goals of therapy for all patients with PsA are as follows, the authors said:
- To achieve the lowest possible level of disease activity in all domains of disease
- To optimize functional status, improve quality of life and well being, and prevent structural damage to the greatest extent possible
- To avoid or minimize complications, both from untreated active disease and from therapy
Those all remain treatment goals, but the options just 5 years ago were fairly limited, the GRAPPA authors noted.
Among their recommendations according to clinical disease domains were conventional disease-modifying drugs (DMARDs) for peripheral arthritis, and moving to TNF inhibitors for nonresponders.
For axial disease, choices included nonsteroidal anti-inflammatory drugs (NSAIDs) and TNF inhibitors. For enthesitis, recommendations included TNF inhibitors or IL-12/23 inhibitors, and for dactylitis, TNF inhibitors could be used.
However, in a table in the article describing the suitability of individual drugs for patients with specific comorbidities ranging from cardiovascular disease to uveitis, by far the most common rating was “NI,” meaning that no information was available.
Research and clinical experience have moved at a rapid pace since the GRAPPA report, and in the past year alone, additional insights have emerged for newer monoclonal antibodies and targeted oral agents.
Targeting IL-23 p19
The monoclonal antibody guselkumab (Tremfya), which targets the p19 subunit of IL-23, was FDA approved for treatment of PsA in 2020, based on the positive results seen in two pivotal phase III trials, DISCOVER-1 and DISCOVER-2.
At the 2021 European League Against Rheumatism virtual congress, an additional study was presented that more fully examined the potential for guselkumab specifically among patients who had not adequately responded or had not tolerated anti-TNF therapy — “a cohort of patients who have significant unmet needs,” explained Laura C. Coates, MBChB, PhD, of the University of Oxford in England, who presented the results.
The study, known as COSMOS, included 285 patients, who “had significant disease activity across domains,” with a mean duration of disease of 8.5 years, she said. Patients were randomized to treatment with subcutaneous guselkumab or placebo at weeks 0 and 4 and then every 8 weeks through week 44. At week 24, patients initially given placebo were crossed over to the active treatment.
By week 48, 20% improvements on the criteria of the American College of Rheumatology (ACR20) responses were seen in 57.7% of patients in the guselkumab/guselkumab group and in 54.9% of those in the placebo/guselkumab arm.
In another study, a post-hoc analysis of enthesitis data from DISCOVER-1, enthesitis had resolved by week 24 in 45% of patients given subcutaneous guselkumab at 100 mg every 4 weeks and in 50% of those given the medication every 8 weeks compared with 29% of those given placebo. After week 24, all patients were receiving the active treatment, and by week 52, enthesitis had resolved in 58% of all patients.
Another monoclonal antibody that targets the IL-23 p19 subunit, tildrakizumab (Ilumya), showed promise for the joint and skin manifestations of PsA in a phase IIb study that enrolled 391 patients with active disease. At week 24, 71.4% to 79.5% of patients randomized to one of several doses of tildrakizumab had ACR20 responses compared with 50.6% of those receiving placebo.
Skin disease as measured on the Psoriasis Area and Severity Index (PASI) showed greater improvements in all active treatment arms at week 24 compared with placebo, and the impact of disease on patients’ lives declined and was sustained through week 52. However, benefits were not seen for enthesitis or dactylitis.
The effects of a third IL-23/p19 inhibitor, risankizumab (Skyrizi), in two clinical trials were presented at the ACR 2021 virtual congress. The studies, which included 1,400 patients who had an inadequate response to DMARDs or other biologics, randomized participants to receive subcutaneous risankizumab at 150 mg or placebo at baseline and at weeks 4 and 16. At week 24, ACR20 responses were observed in 55.5% of patients receiving risankizumab compared with 31.3% of those given placebo.
Also at week 24, PASI 90% improvements were seen in 53.2% of the risankizumab group compared with only 10% of the placebo group. Significantly higher rates for the active treatment also were seen for disability, fatigue, and enthesitis and dactylitis.
JAK and Tyrosine Kinase Inhibition
The oral Janus kinase (JAK) inhibitor upadacitinib (Rinvoq), which is approved for treatment of rheumatoid arthritis, also found benefits in PsA in a phase III trial that compared this medication with placebo and also with the TNF inhibitor adalimumab (Humira).
SELECT-PsA included more than 1,700 patients from 281 sites in 45 countries, and the results were published in the New England Journal of Medicine in April.
At week 12, ACR20 responses were seen in 70.6% of patients given 15 mg upadacitinib daily, 78.5% of those given 30 mg per day, 65% of those receiving subcutaneous adalimumab at 40 mg every other week, and 36.5% of those assigned to placebo. Both upadacitinib doses were considered noninferior to adalimumab, and the 30-mg dose was considered superior.
Also presented at the 2021 ACR virtual meeting, a phase IIb trial assessed effects of the small molecule tyrosine kinase 2/JAK inhibitor brepocitinib for PsA. The study included 218 patients who had active disease despite treatment with NSAIDs and DMARDs; up to one-third also could have previously used a TNF inhibitor. Participants were randomized to receive brepocitinib in daily doses of 10, 30, or 60 mg or placebo.
At week 16, 66.7% of the 30-mg group and 74.6% of the 60-mg group had achieved ACR20 responses compared with 43.3% of the placebo group, and 48.3% and 44.1%, respectively, had ACR50 responses. At week 52, ACR20 responses were seen in 67.6% and 60.9% of patients.
PASI 75 responses were seen in 59% and 69.2% of the 30- and 60-mg groups at week 16 and in 64.2% and 60.8% at week 52. Both of the higher doses also were associated with significant improvements in disease activity and quality of life, and patients in the 60-mg group also had improvements in dactylitis and enthesitis.
Source: MedicalNewsToday.com
