MADRID – When it comes to patients with rheumatoid arthritis who are responding inadequately to methotrexate therapy, results of the Oral Rheumatoid Arthritis triaL (ORAL) Strategy study suggest that adding the Janus kinase inhibitor tofacitinib is just as effective as adding the tumor necrosis factor inhibitor adalimumab.

At 6 months’ follow-up, 46% of patients randomized to tofacitinib (Xeljanz) plus methotrexate met the trial’s primary endpoint of an American College of Rheumatology response of at least 50% (ACR50), compared with 44% of those who were given adalimumab (Humira) plus methotrexate. This result met the trial’s prespecified criteria for noninferiority. An ACR50 response means that there was at least 50% improvement in tender or swollen joint counts as well as a 50% improvement in at least three of the other five criteria (acute phase reactant, such as erythrocyte sedimentation rate; patient assessment; physician assessment; pain scale; and disability/functional questionnaire).

The study also assessed the use of tofacitinib as monotherapy vs. the two combination treatments, but noninferiority was not shown despite monotherapy helping 38% of patients to achieve the primary endpoint.

Nevertheless, “in circumstances where methotrexate is precluded, tofacitinib monotherapy is a clinically viable option,” lead study author Roy Fleischmann, MD, said at the European Congress of Rheumatology.

“This actually substantiates what I’ve done in clinical practice since [tofacitinib] was approved,” said Dr. Fleischmann, a rheumatologist in group practice in Dallas. “If I have patients on methotrexate and they show an incomplete response, I add tofacitinib; I don’t switch, I add. Then if the patient has a good response – a really good response – then I discontinue [methotrexate].”

Dr. Fleischmann said he does the same when adding a tumor necrosis factor inhibitor to methotrexate and that there are some patients who just do better with combination treatment.

ORAL Strategy was a phase IIIB/IV study that randomized 1,152 adults with active RA, despite treatment for more than 4 months with 15-25 mg/kg of methotrexate per week. Patients had to have four or more painful or tender joints and four or more swollen joints at baseline, and a high-sensitivity C-reactive protein level of 3 mg/L or more.

Patients were randomized to one of the study’s three treatment arms: tofacitinib 5 mg twice daily as monotherapy (n = 384), the same regimen of tofacitinib added to methotrexate (n = 376), or adalimumab 40 mg every 2 weeks added to methotrexate (n = 386). (Two patients in each group did not receive their assigned treatment.) Treatment was for 1 year, and concomitant treatment with nonsteroidal anti-inflammatory drugs, oral glucocorticoids, or both was allowed so long as their doses remained stable and no dose adjustments were necessary.

ACR20 responses were also recorded and were achieved by 65% with tofacitinib monotherapy, 73% with tofacitinib plus methotrexate, and 71% with adalimumab plus methotrexate, and ACR70 responses were 18%, 25%, and 21%, respectively. Comparable improvements from baseline to the end of the study were also seen for Simple Disease Activity Index, Clinical Disease Activity Index, Disease Activity Score in 28 joints using erythrocyte sedimentation rate, and Health Assessment Questionnaire scores in patients given the combination treatments.

The study’s findings were published online (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31618-5) to coincide with their presentation in a late-breaking abstract at the meeting.

“The ORAL Strategy trial highlights three benefits from the combination of tofacitinib and methotrexate in active rheumatoid arthritis,” independent commentators David Scott, MD, and Matt D. Stevenson, PhD, wrote in an editorial (Lancet. 2017 Jun 16. doi: 10.1016/S0140-6736[17]31659-8).

“First, this combination’s efficacy and toxicity are similar to injectable biologics such as adalimumab,” said Dr. Scott of King’s College London and Dr. Stevenson of the University of Sheffield (England). Indeed, no new side effects were seen, and side effects were consistent with those seen in previous studies.

“Second,” they wrote, “the onset of action of these drugs seems equally rapid. Third, most patients are able to remain on tofacitinib therapy for 12 months.”

Dr. Scott and Dr. Stevenson suggested these findings are “extremely encouraging” as “they show the ongoing benefits of innovation in drug treatment.”

The findings support the previous RA-BEAM trial (N Engl J Med. 2017;376:652-62) with another Janus kinase inhibitor, baricitinib, Dr. Fleischmann said during his presentation, which had also shown combination therapy with methotrexate was perhaps more beneficial than adding adalimumab.

In the Lancet editorial, Dr. Scott and Dr. Stevenson wrote: “Although a combination of [Janus kinase] inhibitors with methotrexate is likely to be the way they are used in clinical practice, monotherapy results in clinical and functional responses, as shown in the ORAL Strategy trial, and thus might be appropriate in some patients.”

The study was funded by Pfizer. Dr. Fleischmann has received research grants, research support, and consultancy fees from Pfizer and from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Sanofi-Genzyme, and UCB. Dr. Scott has advised Eli Lilly, Roche Products, Napp Pharmaceuticals, Baxalta, and Novartis. Dr. Stevenson did not have any industry disclosures.

Add-on tofacitinib as good as adalimumab for active RA