Inhibition of PsA Radiographic Joint Damage With Secukinumab

Psoriatic arthritis (PsA) radiographic disease progression, quantified by changes in modified total Sharp/van der Heijde scores (SHS) for PsA, was inhibited by secukinumab, a humanized immunoglobulin G1 monocloncal antibody that binds interleukin-17A. This data was derived from the phase 3 trial entitled Efficacy at 24 Weeks and Long Term Safety, Tolerability and Efficacy up to 2 Years of Secukinumab in Patients With Active Psoriatic Arthritis (FUTURE 1 trial, ClinicalTrials.gov identifier: NCT01392326).

In FUTURE 1, patients with PsA were randomized 1:1:1 to receive treatment with either secukinumab 10 mg/kg intravenously (IV) at baseline and at weeks 2 and 4, followed by subcutaneous (SC) administration of either 150 mg or 75 mg secukinumab every 4 weeks, or placebo. After 16 weeks of treatment, patients were re-assessed and classified as a responder if they demonstrated a ≥20% improvement in tender and swollen joint counts from baseline. Patients were permitted to receive concomittant methotrexate (MTX) therapy during this trial. 

Patients assigned to receive placebo who were designated as nonresponders were re-randomized at week 16 to receive either secukinumab 75 mg or 150 mg SC every 4 weeks. Patients receiving placebo who were designated as being responders were started on the same regimen starting at week 24. Patients already receiving secukinumab who were designated as nonresponders continued on current treatment regimen.  

Changes in mean modified total SHS scores, including erosion and joint space narrowing (JSN), were used to determine radiographic progression at baseline, week 16 for nonresponders or week 24 for responders, and finally at week 52. Lack of radiographic progression was defined as a change of ≤0.5 in the modified total SHS, from baseline to week 24, and from week 24 to week 52. 

Six hundred six patients with PsA were randomized to receive treatment outlined above. Compared with patients receiving placebo, those receiving secukinumab had less radiographic PsA progression at 52 weeks.  

In tumor necrosis factor (TNF)-naïve patients, mean changes in modified total SHS from baseline to week 24 were 0.05 for the pooled secukinumab treatment group and 0.57 for the placebo treated group. Radiographic structural progression from week 24 to week 52 in these patients also remained low (mean change in the modified total SHS  −0.01 for patients receiving 150mg and 0.14 for patients receiving 75 mg).

In patients who had received anti-TNF therapy in the past but demonstrated inadequate responses or intolerance to treatment, mean changes in modified total SHS scores from baseline to week 24 were 0.16 and 0.58, respectively.

“A high proportion of patients receiving secukinumab showed no progression (change in SHS of ≤ 0.5) from baseline to week 24 (82.3% of the IV→150 mg group and 92.3% of the IV→75 mg group) and from week 24 to week 52 (85.7% of the IV→150 mg group and 85.8% of the IV→75 mg group),” the authors found. 

Summary and Clinical Applicability

Radiographic disease progression, including erosion, was inhibited by secukinumab in patients with PsA. This effect appeared to persist for up to 52 weeks. Suboptimal secukinumab concentrations was proposed as explanation of why a subset of patients had persistently high evidence of radiographic progression.

Limitations and Disclosures

• Patients designated as nonresponders at week 16 were not re-assessed at week 24, with linear extrapolation used to estimate radiographic data instead
• No radiographic markers of new bone formation was assessed, as only erosions and JSN values were analyzed
• An active comparator trial would be needed to formally assess the effects of concomittant MTX therapy

Reference

Van der heijde D, Landewé RB, Mease PJ, et al. Brief Report: Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage in a Phase III Study of Active Psoriatic Arthritis. Arthritis Rheumatol. 2016;68(8):1914-21.

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