Tofacitinib-induced improvements in RA sustained through 2 years of treatment
Tofacitinib (TFC) yields clinical and radiographic improvements in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), and such improvements are sustained for up to 24 months without new safety signals, according to the results of the phase III ORAL* Scan trial.
ORAL Scan randomized 797 RA patients (mean age, 52 years; 85.07 percent female) on stable background MTX to receive TFC 5 mg (n=321) or 10 mg (n=316) twice daily or placebo. Patients receiving placebo switched to twice-daily TFC at either 5 mg (n=81) or 10 mg (n=79) at month 3 or month 6.
Primary endpoint results from planned interim analyses at month 12 were reported previously. Only 539 patients (67.6 percent) continued treatment after month 12 through to completion of the study at month 24. [Arthritis Rheum 2013;65:559-570]
Responses according to the American College of Rheumatology criteria for 20 percent improvement (ACR20), ACR50 and ACR70 observed at month 12 were maintained through month 24 across all treatment arms. For example, ACR50 response rates with TFC 5 mg and 10 mg were 75.4 percent and 78.5 percent, respectively, at 12 months and remained stable at 73.5 percent and 82.6 percent at 24 months. [Arthritis Rheumatol 2019;doi:10.1002/art.40803]
Likewise, the proportion of patients who achieved remission or low disease activity remained largely unchanged from months 12 through 24 and was comparable across all TFC dosages.
“Similar clinical responses were achieved in patients who received placebo and then switched to TFC and patients who received initial tofacitinib treatment. In general, tofacitinib 10 mg twice daily resulted in numerically higher responses than 5 mg twice daily,” the authors noted.
Majority of the patients (≥90 percent) receiving TFC showed no worsening in structural damage and ≥95 percent did not develop new erosions. Changes in Sharp/van der Heijde and erosion scores from baseline through month 24 were minimal.
“The safety profile and tolerability of tofacitinib through 24 months was consistent with published findings from the 12‐month analysis,” the authors said.
Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity, with the most common being nasopharyngitis and upper respiratory tract infection. There were 11 deaths documented–seven in the TFC 5 mg arm, two in the TFC 10 mg arm and another two in the placebo-to-TFC 5 mg arm—most of which were primary related to cardiovascular events.
However, the authors warned that use of TFC in patients with severe hepatic impairment is not recommended as per the drug's prescribing information and because TFC has not been studied in patients with severe hepatic impairment.
“A potential limitation of this efficacy analysis is that comparison of longer‐term vs shorter‐term data can be challenging when exposure to placebo is limited to early time points, or following termination of the control arm of a study; this is widely acknowledged as a limitation of this type of analysis,” they added.
*Oral Rheumatoid Arthritis (ORAL) Scan trial
** Disease Activity Score in 28 joints using the erythrocyte sedimentation rate