Psoriatic Arthritis Drugs Comparably Improve Joint Outcomes

VIENNA — When it comes to improving joint and skin symptoms in people with psoriatic arthritis (PsA), real-world data suggest that it may not matter too much which class of drug is used.

In the PRO-SPIRIT study, swollen joint counts (SJC), tender joint counts (TJC), and the percentage of patients with a body surface area (BSA) of at least 3% affected by psoriasis were all improved to a similar extent from baseline values at 3 and 12 months by all five drug classes assessed.

This included interleukin (IL) 17A inhibitors, tumor necrosis factor (TNF) inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, and Janus kinase (JAK) inhibitors.

Changes in Clinical Disease Activity index for Psoriatic Arthritis (cDAPSA), which is a composite measure of disease activity that includes SJC, TJC alongside patient pain, patient global assessment, and C-reactive protein levels, also showed relatively similar improvements with the different drug classes.

“Basically, all of these biologics are almost on the same team, in the same field — they all come across as very good,” Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, Leeds, England, told Medscape Medical News.

Ahead of presenting some initial findings from the study at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, McGonagle also said that the data were “very reassuring about the safety.” However, no safety data from the study were revealed during his late-breaking abstract presentation.

‘Agnostic Study’

PRO-SPIRIT is a multinational trial that will run for 2 years. There are six participating countries, namely, Canada, France, Germany, Italy, Spain, and the United Kingdom, and 1192 people with active PsA who started treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) between December 2019 and June 2022.

“It’s a very agnostic study by [Eli] Lilly [& Company],” McGonagle observed. “It’s what I call a very balanced study, where they allowed physicians to start whatever drug they wished in patients with psoriatic arthritis.”

As such, participants are being treated with more than 14 different b/tsDMARDs, which include Lilly’s IL-17A inhibitor ixekizumab (Taltz) as well as secukinumab (Cosentyx); the TNF inhibitors adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade) and its biosimilars; the IL-12/23 inhibitor ustekinumab (Stelara); and the IL-23 inhibitors guselkumab (Tremfya) and risankizumab (Skyrizi).

The largest drug class being used is TNF inhibitors (n = 437), followed by IL-17A inhibitors (n = 507, 67% of whom are taking ixekizumab), JAK inhibitors (n = 124), IL-12/23 inhibitor (n = 34), and IL-23 inhibitors (n = 32). There are also a few patients (n = 32) taking the phosphodiesterase 4 inhibitor apremilast (Otezla), although those data were not included in the presentation.

Heterogeneous Population

As a real-world study, the patient population was heterogeneous, McGonagle acknowledged. While the mean age was about the same, at 52.4 years overall, there were variations in disease duration.

For example, TNF inhibitors were more likely to be given to people earlier in their disease course, at around 6.6 years, whereas both JAK inhibitors and ixekizumab were more likely to be given at 9.0 and 9.2 years, respectively. Secukinumab 150 and 300 mg were initiated at 8.3 and 8.5 years, respectively; ustekinumab at 8.4 years; and IL-23 inhibitors at 8.9 years.

Other differences included the amount of prior treatment. TNF inhibitor users were the least likely to have received prior b/tsDMARDs (31.4%) but the most likely to have received conventional synthetic (cs) DMARDs (53.5%). People treated with IL-17A, IL-23, and JAK inhibitors, on the other hand, were more likely (70.3%-80.8%) to have had prior b/tsDMARDs.

Improvements Across the Board

Reductions in SJC from baseline to 3 months were −2.6 for ixekizumab, −2.1 for secukinumab 150 mg, and −1.8 for secukinumab 300 mg. Values at 12 months were a respective −3.1, −3.3, and −1.1.

The 3- and 12-month reductions in SJC for the other drug classes were a respective −2.8 and −3.5 for TNF inhibitors, −3.1 and −3.9 for JAK inhibitors, −0.9 and −2.7 for the IL-12/23 inhibitor, and −3.1 and −3.9 for IL-23 inhibitors.

A similar pattern was seen with TJC reduction at 3 and 12 months: −4.5 and −5.5 for ixekizumab, −4.5 and −4.6 for secukinumab 150 mg, −3.2 and −4.5 for secukinumab 300 mg, −4.7 and −6.3 for TNF inhibitors, −1.1 and −3.6 for IL-12/23 inhibitor, −5.1 and −6.8 for IL-23 inhibitors, and −5.1 and −7.7 for JAK inhibitors.

Declines in cDAPSA at 3 and 12 months were −11.2 and −12.5 for ixekizumab, −11.7 and −12.8 for secukinumab 150 mg, −7.4 and −7.3 for secukinumab 300 mg, −11.1 and −13.8 for TNF inhibitors, −3.7 and −9.6 for IL-12/23 inhibitor, −8.4 and −11.6 for IL-23 inhibitors, and −10.8 and −14.2 for JAK inhibitors.

McGonagle reported that there were differences in the proportion of patients with high and low disease activity according to the cDAPSA at 12 months. The highest percentages of patients with high disease activity were recorded with secukinumab 300 mg (16.4%) and IL-12/23 inhibitors (16.0%) groups, whereas more patients treated with TNF inhibitor (22.1%) and ixekizumab (19.3%) had a cDAPSA of 0, indicating remission.

As for skin symptoms, respective reductions from baseline BSA at 3 and 12 months were −4.0 and −4.9 for ixekizumab, −2.2 and −2.1 for secukinumab 150 mg, −5.7 and −6.8 for secukinumab 300 mg, −2.6 and −3.4 for TNF inhibitors, −2.9 and −5.0 for IL-12/23 inhibitor, −4.1 and −4.6 for IL-23 inhibitors, and −1.6 and −2.7 for JAK inhibitors.

‘Good Outcomes,’ but Nothing New

Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, gave Medscape Medical News his first impression after seeing the data.

“Without looking at things in detail, what struck me was how poorly IL-23 inhibitors performed,” Maksymowych said.

To him, the outcomes with the different drug classes appeared “very similar except for IL-23, which seemed to be consistently a little bit less across all outcome domains,” which does “not really” fit with the available trial data, he said.

These data do not add much to what is already known, Laura Coates, MBChB, PhD, a clinician scientist and senior clinical research fellow at the University of Oxford in Oxford, England, told Medscape Medical News separately.

“It showed that all of the drugs did pretty well in terms of joint outcomes,” she said.

Coates added, “Even though it’s a prospective study with good outcomes, there’s still a channeling bias because it’s just patients who were started on these drugs for whatever reason.”

For example, “there’s more first-line [treatment] with TNF inhibitors; people with bad skin are probably more likely to have an IL-17 or an IL-23 inhibitor. So, there’s a lot of differences between those patients, which makes it hard to compare.”

Overall, these data were unlikely to make “a massive difference in terms of what we would do or really change how we would choose drugs,” Coates suggested.

PRO-SPIRIT was sponsored by Eli Lilly and Company. McGonagle reported consulting fees, speaker honoraria, research grant support, and/or travel support from AbbVie, Almirall, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB.

Coates received speaking fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Medac, Novartis, Pfizer, and UCB; served as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, MoonLake, Novartis, Pfizer, and UCB; and received grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB.

Maksymowych received research funding, grant support, and honoraria for serving as a consultant to multiple pharmaceutical companies, including AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB. He is chief medical officer of CARE Arthritis Limited.

Sara Freeman is a medical journalist and writer based in London. She is a regular contributor to Medscape Medical News, Medscape News UK, and other specialist healthcare media outlets.