Tofacitinib safe, efficacious in ankylosing spondylitis regardless of baseline CRP

Tofacitinib demonstrates greater efficacy than placebo at week 12 in patients with ankylosing spondylitis (AS) regardless of their baseline C-reactive protein (CRP) levels, a study has shown.

In addition, the safety profile of the study drug is consistent with previous studies of tofacitinib in AS patients, with a higher incidence of treatment-emergent adverse events (TEAEs) and infections in those with CRP <5 mg/L.

“Elevated baseline CRP level in patients with AS could be used as a predictor for rapid treatment response to tofacitinib,” the researchers said.

This study used phase II and phase III data from patients with active AS. The research team stratified endpoints, including 20-percent and 40-percent improvement in Assessment of SpondyloArthritis international Society (ASAS), AS Disease Activity Score with CRP low disease activity, 50-percent improvement in Bath AS Disease Activity Index (BASDAI50), and patient-reported outcomes (PROs), by baseline CRP level: <5 (normal), ≥5 (elevated), <10, and ≥10 mg/L.

Additionally, the researchers assessed safety outcomes between subgroups of patients with normal and elevated baseline CRP levels.

A total of 372 patients were analysed (≥5 mg/L: 69.6 percent; ≥10 mg/L: 50.8 percent). In the <5 mg/L group, more patients treated with placebo received concomitant NSAIDs or sulfasalazine (SSZ) than those treated with tofacitinib at baseline. [J Rheumatol 2024;51:772-780]

At week 12, tofacitinib treatment resulted in generally higher efficacy and PRO responses when compared with placebo, regardless of baseline CRP. The treatment effect (placebo-adjusted response) was numerically higher in ≥5 and ≥10 mg/L groups than in <5 and <10 mg/L groups.

Furthermore, the incidence rates of TEAEs and “all infections” were numerically greater with tofacitinib than with placebo in patients with baseline CRP <5 mg/L. However, such rates were comparable between tofacitinib and placebo in those with CRP ≥5 mg/L.

“The higher concomitant NSAID/SSZ exposure in the baseline <5 mg/L placebo group may have improved efficacy responses in this group, and ultimately may have affected the tofacitinib treatment effect,” the researchers said.

An earlier study has examined the effect of baseline CRP level on the efficacy of tofacitinib, but the high-sensitivity CRP cutoff of 2.87 mg/L used in the current analysis may not be considered clinically relevant. [Ann Rheum Dis 2017;76:1340-1347]

“In this study, we focused on the higher CRP cutoffs of 5 and 10 mg/L to evaluate the efficacy of tofacitinib,” the researchers said. “Similar CRP cutoffs (5‒10 mg/L) have been used previously in other studies with TNFi and IL-17 inhibitors in patients with AS.” [Arthritis Rheumatol 2020;72:0904; Arthritis Rheum 2009;61:1484-1490; Rheumatology 2018;57(suppl 6):1-3]

The current finding that tofacitinib was more efficacious than placebo irrespective of baseline CRP level in AS patients supports that of prior studies on IL-17 inhibitors and TNFi. [Arthritis Rheumatol 2020;72:0904; Arthritis Rheum 2009;61:1484-1490; Rheumatology 2018;57(suppl 6):1-3]

“Longer-term, prospective, and real-world data would be required to fully establish the effect of baseline CRP level on the efficacy and safety of tofacitinib in patients with AS,” the researchers said.