Inhibition of radiographic progression across levels of composite index-defined disease activity in patients with active psoriatic arthritis treated with intravenous golimumab: results from a phase-3, double-blind, placebo-controlled trial

Abstract

Background: In the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment.Methods: In this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2 mg/kg (N = 241; week 0, week 4, every 8 weeks [q8w]) or placebo (N = 239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed. Results: Across indices, golimumab-treated patients demonstrated less radiographic progression than placebotreated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were − 0.83 vs. 0.91, respectively, in patients achieving MDA and − 0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placeborandomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab-vs. placebo→golimumab-treated patients achieving MDA were − 1.16 vs.

Secukinumab improves physical function and quality of life and inhibits structural damage in patients with PsA with sustained remission or low disease activity: results from the 2-year phase 3 FUTURE 5 study

“…Thus, there is a potential ‘disconnect’ between disease activity and radiographic progression, highlighting that secukinumab may have a protective effect on structural damage progression in PsA that is independent of achievement of sustained LDA or REM. This was also observed in previous adalimumab 30 31 and golimumab studies 23 in PsA patients. In the ADEPT trial, changes in mTSS were significantly lower with adalimumab, even in patients having moderate or high disease activity or not achieving MDA.…”

“… 30 Similarly in the GO-VIBRANT trial, golimumab-treated patients exhibited less radiographic progression regardless of composite index or disease activity state achieved. 23 Patients with rheumatoid arthritis have also reported this ‘disconnect’ phenomena with other TNFi therapies, abatacept and IL-6i. 32–35 …”

Psoriatic arthritis: one year in review 2022

“…Possibly due to a direct GOL effect in reducing osteoclast activity, the treatment of PsA patients with IV-GOL showed a significant improvement in the erosive burden of the disease, with a reduction of radiographic progression, even in those patients who did not achieve LDA status (57).…”