The study found the mean changes in DAS28-ESR in the patients treated by tocilizumab monotherapy compared with those treated with combined methotrexate and tocilizumab were 0.46 (95% CI, 0.22, 0.70) and 0.14 (95% CI, -0.11, 0.39), respectively, with an adjusted difference of 0.318 (95% CI, 0.045, 0.592), demonstrating that discontinuing methotrexate was noninferior to the combined therapy.
The study also found similar safety between the two treatment arms, with patients treated with combination methotrexate plus tocilizumab experiencing a slightly higher incidence of adverse events compared with tocilizumab monotherapy. The total number of adverse events per 100 patient-years was 308.07 (95% CI, 272.98, 346.43) and 238.00 (207.58, 271.61), respectively. Of the serious adverse events, infection was the most common, occurring in 2.1% and 2.2% in patients treated with tocilizumab monotherapy and those treated with combined therapy, respectively.
‘This is one of the first studies showing that methotrexate may be discontinued in a cohort of patients with a biologic agent without experiencing a significant predefined disease flare.’ —Joel Kremer, MD
What Does This Mean for Patients?
These results provide a good option for patients who prefer not to stay on methotrexate or are intolerant to it. “If a patient is on the combination of tocilizumab and methotrexate, they may be able to streamline their treatment by discontinuing methotrexate,” says Dr. Kremer. “Most patients would rather take fewer meds.”
However, he cautions that “as with all clinical situations involving changes in treatment, the patient should be followed closely.”
Dr. Weinblatt also says the results offer patients who don’t want to stay on methotrexate the option of stopping the combination therapy and continuing on tocilizumab monotherapy, with many patients able to maintain a good positive response.
However, he also provides several caveats on issues he says were not addressed in the study. Among these were whether a patient can obtain a sustained positive response from discontinuing methotrexate by lowering its dose rather than abruptly stopping it, as was done in the study.
“Another important question is whether you can maintain the positive response of methotrexate plus tocilizumab by stretching out the interval of tocilizumab dosing (e.g., weekly to every other week or every two weeks to every three weeks),” he says. “This had implications on the cost of therapy, which is a critical issue.”
Finally, Dr. Weinblatt points out another study finding: Although DAS28-ESR scores were similar between the two treatment groups at 24 weeks, the response rates of patients randomized to tocilizumab monotherapy who achieved ACR20/50/70 responses from baseline to Week 24 were about 8–11% lower than those randomized to the combination therapy.
