EULAR 2015: RA Research Shows Imperfect Guidelines, Suggests Strategies with Biologics

Studies suggest that methotrexate use boosts the effectiveness of biologics.
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ROME, Italy—Even with classification criteria that have been updated and refined over time, rheumatoid arthritis is still a diagnosis that ultimately has to be made with clinical judgment, said Ronald van Vollenhoven, MD, PhD, professor of medicine and chief of clinical therapy research in inflammatory diseases at the Karolinska University in Sweden. His remarks came during a review of new literature at EULAR 2015, the annual congress of the European League Against Rheumatism (EULAR).

Sensitivity Challenges

Studies on the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) seem to show that they are not as sensitive as the 1987 criteria, even though one of the intentions of the newer criteria was that they were going to be more sensitive, Dr. van Vollenhoven said. Studies have also found that agreement is “not great” between the older criteria, the newer criteria and expert opinion.¹

Also, patients identified with the newer criteria seem to have lower progression rates than those identified using the older ones, he said.

“The patients who fulfilled the newer criteria do not necessarily have as bad a prognosis as those who fulfilled the previous criteria,” he said. “The 2010 criteria might be identifying slightly milder (diseased) patient populations.”

A systematic literature review late last year, in which RA cases identified using the 2010 criteria were then subjected to expert opinion, found that the sensitivity rate of the criteria was 80% and the specificity rate was just 60%. So a declaration that someone has RA, based on the criteria, would be wrong 1 in 5 times. And a declaration that someone does not have RA would be wrong 2 in 5 times, he said.²

“I do not think that you have to completely base your decision on those criteria,” Dr. van Vollenhoven said. “You should use clinical judgment.”

Importance of Imaging

A study last year found that using MRI along with the 2010 criteria improves the diagnostic probability of early RA, he noted.

“I think imaging is going to become more and more important as an ancillary diagnostic tool,” he said.

Imaging is going to become more & more important as an ancillary diagnostic tool.

Studies out of his center have found that musculoskeletal ultrasound can improve diagnostic certainty and found that a 12-biomarker panel, known as the MBDA, can help predict which patients will respond better to biologic therapy and which will respond better to non-biologic DMARD therapy.^3-5

In the end, though, he said, “No set of criteria and no imaging modality and no biomarkers are ever going to be able to replace a clinical judgment by an experienced clinician.”

Methotrexate & Prednisone

In a talk on the therapeutic landscape of RA, Joao Fonseca, MD, professor of rheumatology at the University of Lisbon, drew attention to recent studies showing the value of early use of methotrexate plus prednisone, and that they tend to perform well compared with biologics when used early.⁶

Also, in one trial, researchers showed that early use of a regimen starting methotrexate plus just 30 mg/day of prednisone was not inferior—with regard to disease activity in patients with moderate disease—to a regimen starting with 60 mg/day of prednisone, along with methotrexate and sulfasalazine.⁷

With methotrexate and prednisone, “the earlier—the sooner—the better,” Dr. Fonseca said.

With Biologics

Studies over the past year have also supported the idea that methotrexate use boosts the effectiveness of biologics. A study out of Japan, for example, showed that concomitant use of methotrexate with tocilizumab increased the chances of high-disease-activity patients achieving remission.⁸

He said that recent studies suggest that biosimilars can bring about similar efficacy at a reduced cost. Last year, a biosimilar was included for the first time in a meta-analysis on biologics for ankylosing spondylitis, and the infliximab biosimilar was found to have similar efficacy and safety.⁹

But Dr. Fonseca said that when prices for bio­similars are negotiated, potential increases in dosing and frequency of administration of a biologic therapy have to be taken into account, because those fluctuations in treatment strategy come with increased costs. A study out of Greece looked at real-life use of etanercept, infliximab and adalimumab and highlighted the resulting price differences.¹⁰

“Many of these patients have to adjust dose [and] frequency, and by doing that, the price increases,” he said. “[Thus], the annual overall cost of infliximab will exceed the [cost] of etanercept. To negotiate a price of a biosimilar of infliximab, you have to [take] this into consideration.”

Thomas R. Collins is a freelance medical writer based in Florida.

References

1. Burgers LE, van Nies JA, Ho LY, et al. Long-term outcome of rheumatoid arthritis defined according to the 2010-classification criteria. Ann Rheum Dis. 2014 Feb;73(2):428–432.
2. Radner H, Neogi T, Smolen JS, et al. Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: A systematic literature review. Ann Rheum Dis. 2014 Jan;73(1):114–123.
3. Razaei H, Torp-Pedersen S, af Klint E, et al. Diagnostic utility of musculoskeletal ultrasound in patients with suspected arthritis—A probabilistic approach. Arthritis Res Ther. 2014 Oct 1;16(5):448.
4. Hambardzumyan K, Bolce R, Saevarsdottir S, et al. Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: Results from the SWEFOT trial. Ann Rheum Dis. 2015 Jun;74(6):1102–1109.
5. Hambardzumyan K, Bolce R, Saevarsdottir S, et al. In early rheumatoid arthritis, the multi-biomarker disease activity score at different time-points is predictive of subsequent radiographic progression (Abstract 364). The 2014 ACR/ARHP Annual Meeting, Nov. 15–19, 2014, Boston.
6. Verschueren P, De Cock D, Corluy L, et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: The CareRA trial. Ann Rheum Dis. 2015 Jan;74(1):27–34.
7. strategy: Clinical results after 26 weeks. Ann Rheum Dis. 2014 Jun;73(6):1071–1078.
8. Kojima T, Yabe Y, Kaneko A, et al. Importance of methotrexate therapy concomitant with tocilizumab treatment in achieving better clinical outcomes for rheumatoid arthritis patients with high disease activity: An observational cohort study. Rheumatology (Oxford). 2015 Jan;54(1):113–120.
9. Baji P, Péntek M, Szántó S, et al. Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis. Eur J Health Econ. 2014 May;15 Suppl 1:S45–S52.
10. Fragoulakis V, Vitsou E, Hernandez AC, et al. Economic evaluation of anti-TNF agents for patients with rheumatoid arthritis in Greece. Clinicoecon Outcomes Res. 2015 Jan 16;7:85–93.