Greater Pre-Existing Radiographic Damage in Psoriatic Arthritis May Reduce Chance of Full Inhibition With Secukinumab

An analysis of 2 phase 3 studies of secukinumab (Cosentyx, Novartis) in patients with psoriatic arthritis (PsA) showed substantial prevalence of radiographic damage at baseline that was related to time since diagnosis. Moreover, pre-existing radiographic damage was associated with a patient’s individual joint activity status. The results, which were published in Arthritis Research & Therapy,¹ also showed that patients with the greatest baseline radiographic damage had a reduced likelihood of achieving zero joint count status.

“Secukinumab therapy, in a dose dependent manner, was associated with inhibition of joint tenderness and swelling, although high radiographic damage at baseline was associated with reduced likelihood of full inhibition,” investigators, led by Philip Mease, MD, director of rheumatology research at the Swedish Medical Centre in Providence St Joseph Health and professor at University of Washington, Seattle, wrote.

The analysis included pooled data from the FUTURE 1 and FUTURE 5 studies, with a total of 1554 patients. Investigators aimed to quantify the baseline prevalence of pre-existing radiographic damage and assess the association of this damage with baseline swollen/tender joint counts (SJC/TJC). They also assessed the correlation between baseline radiographic damage and secukinumab response.

Baseline radiographic bone erosion and joint space narrowing scores were collated at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and SJC/TJC in the same joints at several visits. Radiographic damage was assessed for the overall patient and for individual joints, along with bone erosion and joint space narrowing scores. The association between joint tenderness and swelling and vdH-mTSS was assessed at the overall patient individual joint-levels. The response to secukinumab treatment was assessed using SJC/TJC at weeks 16 and 52. The proportion of patients achieving minimal disease activity (MDA) over all assessments within 1 year was assessed from FUTURE 5 alone.

Pre-existing radiographic damage with erosion was more prevalent than with joint space narrowing, with positive erosion and joint space narrowing scores seen in 86% and 60% of patients, respectively. The results also showed that a higher prevalence of radiographic damage was associated with a longer time since PsA diagnosis. Joint tenderness and swelling were “weakly” associated with radiographic damage at baseline at the patient-level, but “strongly” associated at the individual joint-level, with a greater probability of tender/swollen joints to associate with higher joint space narrowing/erosion scores, investigators reported.

The analysis also showed that secukinumab reduced TJC and SJC across all values of baseline erosion and joint space narrowing scores at weeks 16 and 52. Patients with greater radiographic damage were less likely to achieve zero tender/zero swollen joint status and had lower chance of achieving MDA.

As the analysis used cross-sectional data and not on a complete follow-up of patient journeys, “clear statements cannot be made about whether erosion manifests before joint space narrowingin patients with PsA, even though a higher prevalence of erosion than joint space narrowing was observed in these patients,” investigators concluded.

Reference:

Mease P, van der Heijde D, Kirkham B, et al. Quantification of pre-existing radiographic damage and its relationship with joint activity and long-term clinical outcomes with secukinumab therapy in patients with psoriatic arthritis. Arthritis Res Ther. 2022;24(1):283. Published 2022 Dec 28. doi:10.1186/s13075-022-02944-1