A Look at Personalized Therapy for Psoriatic Arthritis

Researchers are taking first steps into personalized medicine approaches for treating psoriatic arthritis (PsA), but challenges remain, and further study is needed.

A report in Expert Review of Clinical Immunology explored immunophenotyping, saying the proof-of-concept approach is “novel and exciting” and provides a potential path toward more precise treatment of PsA.

PsA is a progressive inflammatory syndrome associated with psoriasis and has various manifestations. These include inflammatory arthritis, as well as inflammation of the spine, the sites where tendons or ligaments insert into the bone, and the fingers and toes. PsA occurs in up to 30% of individuals with psoriasis. Although recent years have seen a swift expansion of therapeutic options available, much remains to be learned on identifying which medicines are more effective for individual patients, the authors said.

The authors called for large, carefully designed trials combined with complex algorithms to explore the efficacy of tissue and blood analysis in patients with PsA for immunophenotyping. But they cautioned against the obstacles. Tissue analysis is more specific, but also more expensive and invasive, while blood analysis is more practical but may give incomplete information.

Current practice generally calls for starting treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), followed, if response is inadequate, by biologic disease-modifying antirheumatic drugs (bDMARDs). Newer guidelines form the American College of Rheumatology (ACR) and National Psoriasis Foundation call for using bDMARDs as a first-line treatment—specifically, tumor necrosis factor alpha inhibitors (TNFi), according to the authors.

Other bDMARDs are available besides TNFi: interleukin-17A (IL-17A) inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors. In addition, there are 2 small molecule targeted-synthetic disease-modifying antirheumatic drugs (tsDMARDS) in the toolbox: janus kinase inhibitors and apremilast (Otezla), a phosphodiesterase 4 inhibitor, authors explained.

However, some patients with inadequate responses to TNFi will respond to other bDMARDs, while other cases require usage of drugs with a different mode of action, the authors said. Such unpredictability can delay relief. Furthermore, bDMARDs carry the risk of reactivation of latent tuberculosis, opportunistic infections, and skin site reactions from drug infusion or injection.

Decisions for bDMARDs and tsDMARDS are generally based on phenotype, musculoskeletal or dermatologic manifestations, along with clinician familiarity and cost, the authors said.

One open-label trial addressed personalized medicine in PsA, evaluating bDMARD treatments based on patients’ baseline T-helper (T_H) cell immunophenotypes against those on standard treatments. There were significant decreases from baseline in a measure of disease activity compared with those on standard treatment, but there was no significant difference in Psoriasis Area and Severity Index (PASI) scores. Even so, the authors said, they considered T_H cell immunophenotyping promising.

Some direct comparisons among bDMARD therapies have been conducted. A 52-week trial (SPIRIT head-to-head [NCT03151551]) compared the efficacy of ixekizumab (Taltz; IL-17A inhibitor) and adalimumab (Humira; TNFi) in bDMARD-naïve patients with active PsA. Ixekizumab was superior, as a significantly higher proportion of patients achieved combined ACR50 (50% improvement from baseline in ACR responses) and PASI-100 responses (39.2% vs. 26.1%, respectively; P < .001).

But when another IL-17A inhibitor, secukinumab (Cosentyx), was compared with adalimumab in a phase 3b trial (EXCEED; NCT02745080), neither drug was found superior to the other.

The ACCEPT phase 3 trial (NCT00454584) compared the efficacy of ustekinumab (Stelara; IL-12/23 -p40 subunit inhibitor) with etanercept (Enbrel; TNFi) in the treatment of moderate-to-severe psoriasis at 12 weeks. Significantly higher proportions of patients on ustekinumab achieved PASI-75 responses, when compared with the TNFi and placebo (P = .01 and P < .001, respectively).

The CLEAR phase 3b study (NCT0274982) established secukinumab as superior in achieving PASI-90 and PASI-100 responses (P <.0001 and P =.0103, respectively), in patients with moderate-to-severe psoriasis, when compared with ustekinumab.

Reference

White JPE and Coates LC. The road to personalised medicine in psoriatic arthritis. Expert Rev Clin Immunol. Published online May 18, 2021. doi:10.1080/1744666X.2021.1931125