medwireNews: Most patients with rheumatoid arthritis (RA) who achieve low disease activity with the Janus kinase (JAK) inhibitor tofacitinib plus methotrexate can withdraw methotrexate without significant worsening of disease activity, findings from the ORAL Shift trial show.
“We know that […] 30% of patients in the States who are on tofacitinib with methotrexate withdraw methotrexate many times on their own, so we wanted to see what would happen clinically,” lead researcher Stanley Cohen (Metroplex Clinical Research Center, Dallas, Texas, USA) explained at the EULAR 2019 congress in Madrid, Spain.
The study involved 530 patients with moderate-to-severe RA who after taking tofacitinib modified release (MR) 11 mg/day formulation with methotrexate for 24 weeks had achieved low disease activity, based on a CDAI score of 10 points or below.
Prior to this the patients had received oral methotrexate 15─25 mg/week continuously for at least 4 months and been taking a stable dose with supplemental folic acid for at least 4 weeks.
The participants were then randomly assigned (double-blind) to continue with the combined treatment (n=266) or switch immediately to tofacitinib MR 11 mg/day plus placebo (n=264) for a further 24 weeks.
From week 24 to week 48, the least squares mean increase in DAS28-ESR was 0.30 points (0.20─0.46) among patients taking tofacitinib monotherapy, which being below the upper bound of the 95% confidence interval of 0.6 was noninferior to the 0.0 points (–0.10 to 0.16) change seen among patients continuing on combined therapy.
In support of this, the average 3-point decrease in DAS28-ESR, from about 6 to 3 points, that was seen prior to randomization was maintained regardless of withdrawal.
Other secondary endpoints included ACR20 and 70 responses, which Cohen said were similar between the tofacitinib monotherapy and combined groups at week 48 (73.1 and 79.7% and 37.9 and 42.9%, respectively), as was the proportion of patients with a decrease in HAQ-DI score of at least 0.22 points (68.6 and 75.2%, respectively), whereas ACR50 response rates were lower with monotherapy versus combined treatment (55.3 and 67.3%, respectively).
The low disease activity rates, based on CDAI scores of 10 points or below, at 48 weeks were numerically lower in patients taking tofacitinib monotherapy compared with combination therapy, at 65.2% versus 77.1%, but remission rates (CDAI of 2.8 points or below) were similar, at 28.4 % and 30.8%, respectively.
“This compliments what we have seen with other biologics such as tocilizumab…”
Click through to watch Stanley Cohen’s comments
Cohen said there were no new safety signals based on what is already known for tofacitinib and JAK inhibitors, and “discontinuations were similar,” at a rate of 1.9% for both treatment groups. “There was a trend for an increase in LFTs [liver function tests] with combination therapy as seen previously,” he added. Cohen also pointed out that there were three pulmonary embolisms – one in the monotherapy group and two in the combined group, while there were two cases of deep vein thrombosis in the combination group. Rates of serious infections and herpes zoster were low in both groups.
Cohen concluded: “As is seen with biologic DMARDs, now with the targeted synthetic DMARD tofacitinib most patients with RA with moderate-to-high disease activity receiving combination therapy, who achieve low disease activity and cannot tolerate or prefer not to use methotrexate, may discontinue [methotrexate] without a significant worsening of disease activity or unexpected safety issues.
“And this data is clinically meaningful to support the dosing regimen options for people on tofacitinib and clinicians managing patients.”
By Lucy Piper
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Ann Rheum Dis 2019; 78: 260–261 (abstract)
European Congress of Rheumatology 2019; Madrid, Spain: 12–15 June