Biologics Comparison in Rheumatoid Arthritis Surprises

Damian McNamara

June 20, 2017

MADRID — For patients with rheumatoid arthritis who do not respond to a tumor necrosis factor (TNF) inhibitor, rituximab or tocilizumab might be more effective than abatacept, results from a new study suggest.

In contrast, for such patients not previouslty treated with a TNF inhibitor, outcomes with the three agents appear to be similar.

"My clinical colleagues think it is a bit surprising that tocilizumab is doing so well," Thomas Frisell, PhD, an epidemiologist from the Karolinska Institute in Stockholm, said here at the European League Against Rheumatism (EULAR) Congress 2017.

"It has been a less popular option in Sweden, which is why they are surprised," he explained.

"Since I'm not a practicing rheumatologist, I have to be careful what I say," Dr Frisell joked with Medscape Medical News. "I know many of my clinical colleagues don't trust the data as much as I do, being the data cruncher on this study."

In many guidelines, the effectiveness of abatacept, rituximab, tocilizumab, and TNF inhibitor biologic disease-modifying anti-rheumatic drugs (DMARDs) as second-line therapy is considered equal. However, the recommendations are based on separate randomized controlled trials and few direct comparisons, Dr Frisell pointed out.

For their study, he and his colleagues compared 12-month outcomes for 6664 patients who initiated therapy with abatacept, rituximab, tocilizumab, or a TNF inhibitor from 2010 to 2014. Study follow-up was approximately 1 year.

Patients in the abatacept, rituximab, and tocilizumab groups tended to be older and of lower socioeconomic status than those in the TNF inhibitor group, and were more likely to have a history of malignancy, serious infections, or diabetes. Despite this, treatment outcomes were generally better with a non-TNF inhibitor, especially rituximab and tocilizumab.

Table 1. Outcomes Associated With First DMARD

Outcome Abatacept, % (n = 240) Rituximab, % (n = 654) Tocilizumab, % (n = 202) TNF Inhibitor, % (n = 5568)
Good EULAR response 34 31 53 26
Improvement on health assessment questionnaire 37 39 45 27
28-joint count score of 0 23 22 31 20


"What's interesting about this study is that when we evaluate the non-anti-TNF biologics, when used as a first biologic DMARD, rituximab and abatacept look equally effective," said Xavier Teitsma, MD, from University Medical Center Utrecht in the Netherlands.

"However, when a patient had already received a TNF inhibitor," he continued, "rituximab was more effective than abatacept."

Table 2. Outcomes After Switch From First-Line TNF Inhibitor

Outcome Abatacept, % (n = 256) Rituximab, % (n = 408) Tocilizumab, % (n = 320) TNF Inhibitor, % (n = 1840)
Good EULAR response 15 24 37 11
Improvement on health assessment questionnaire 20 34 32 17
28-joint count score of 0 11 21 20 12


"This nationwide study shows that for patients who fail a first TNF inhibitor, you are better to switch to rituximab than abatacept," Dr Teitsma told Medscape Medical News. "And the effectiveness of tocilizumab stays the same, regardless of whether a patient received pretreatment. That is the most interesting point."

This is certainly in line with recent treatment recommendations.

"This is certainly in line with recent treatment recommendations," said Dr Frisell. "In their last round of updates, EULAR said as your first biologic you can consider anti-TNFs or non-anti-TNFs, and that essentially, there really is no difference between the effect or safety profiles."

Previously, EULAR strongly recommended initiating treatment with a TNF inhibitor because there were more data to justify their use, he explained. Now, more data are accumulating on non-TNF inhibitors.

In terms of potential limitations, the study did not assess differences in safety or long-term outcomes, nor did it assess lifestyle differences or patient treatment preferences.

Future research is warranted to confirm these findings, Dr Frisell said.

The ARTIS registry used in this study has been or is supported by agreements with AbbVie, BMS, MSD, Pfizer, Roche, Samsung, and UCB. Dr Frisell and Dr Teitsma have disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2017: Abstract FRI0213. Presented June 16, 2017.


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