Tofacitinib Monotherapy Acceptable When Methotrexate Is Inadequate to Patient Response

deformed woman's hands from rheumatoid arthritis
deformed woman’s hands from rheumatoid arthritis
Researchers compared patient-reported outcomes after treatment with tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate in the ORAL Strategy trial.

Tofacitinib monotherapy may be considered for patients who are inadequate responders to methotrexate treatment in rheumatoid arthritis (RA), according to research results published in RMD Open.        

Researchers conducted a 1-year, triple-dummy, active comparator, head-to-head, randomized controlled ORAL Strategy trial ( Identifier: NCT02187055), a phase 3B/4 clinical trial assessment of noninferiority between tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate.

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In total, 1152 patients were randomly assigned 1:1:1 to 1 of 3 treatment arms; 1146 patients were included in the full analysis (tofacitinib monotherapy, n=384; tofacitinib plus methotrexate, n=376; adalimumab plus methotrexate, n=386). Across all patient groups, the mean disease duration ranged from 7.5 to 8.4 years, mean tender joint count in 28 joints ranged from 15.2±6.7 to 15.6±6.5, mean swollen joint count in 28 joints ranged from 11±5.4 to 11.8±5.7, and mean Disease Activity Score in 28 joints ranged from 6.5±0.9 to 6.6±0.9.

At baseline, patient-reported outcomes were similar between treatment arms. Over time, substantial improvements were reported in all arms, with the majority of patients reporting improvements greater than the minimum clinically important differences.

Investigators noted clinically meaningful improvements at week 6 (least squares mean [LSM] change for tofacitinib monotherapy, -26.1; tofacitinib plus methotrexate, -28.2; adalimumab plus methotrexate, -26.6). At 3 months, these values were higher in the tofacitinib plus methotrexate group compared with the tofacitinib monotherapy group. Similar improvements in Patient Global Assessment of disease activity were reported in both combination arms compared with tofacitinib monotherapy at 6 months (LSM change, -35.7, -38.4, and -38.8, respectively).

Clinically meaningful pain improvements were reported across all treatment groups at week 6 (LSM change, -22.6, -22.8, and -23.0, respectively). These improvements generally approached maximal values by month 3. Tofacitinib plus methotrexate therapy led to greater improvements from baseline vs tofacitinib monotherapy at 3 months, sustained at 6 and 12 months.

No statistically significant LSM changes from baseline were reported at any time point between all treatment arms in the Health Assessment Questionnaire-Disability Index. Improvements reached maximal values by month 3 and continued to month 12 for all treatments.

Functional Assessment of Chronic Illness Therapy-Fatigue changes from baseline were similar between the tofacitinib groups at all time points. Improvements were comparatively lower in the adalimumab plus methotrexate group at months 3 and 6.

Compared with the tofacitinib monotherapy group, the tofacitinib plus methotrexate group demonstrated greater improvements in the 35-Item Short-Form Health Survey physical component summary, sustained through months 6, 9, and 12. A greater percentage of patients reported improved results in the tofacitinib plus methotrexate group compared with the adalimumab plus methotrexate group at month 3, compared with tofacitinib monotherapy.

Study limitations included the potential generalizability of observations, lack of data from time points earlier than 6 weeks, and enrollment of a majority of patients only from countries with low accessibility to disease-modifying antirheumatic drugs and randomized controlled trials.

“These [patient reported outcomes] data suggest that in patients without sufficient responses to, or who are intolerant to, [methotrexate], tofacitinib monotherapy can be an effective alternative treatment,” the researchers concluded. “Future research to identify subsets of patients that consistently show improvements in all, or specific, [patient reported outcomes], warrants consideration, to determine tailored treatment approaches for [methotrexate-intolerant response] patients with RA.”

Disclosure: This study was supported by Pfizer Inc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures. .


Strand V, Mysler E, Moots RJ, et al. Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial [published online October 1, 2019]. RMD Open. doi:10.1136/rmdopen-2019-001040