Conference Coverage

Three-drug combo keeps early RA at bay long term



– A triple combination of methotrexate, hydroxychloroquine, and triamcinolone used to induce remission in patients with early rheumatoid arthritis (RA) was associated with higher long-term remission rates than methotrexate used alone in a study presented at the European Congress of Rheumatology.

The percentages of patients in remission were a respective 88.2% versus 72.1% at 1 year, 86.6% versus 81.9% at 2 years, and 88.0% versus 85.8% at 3 years.

“Combination treatment results in a higher remission rate in the first 2 years of treatment and a similar remission rate in the third year,” said Tammo Brunekreef, a medical student at Ziekenhuisgroep Twente in Almelo, the Netherlands, who presented the findings.

Tammo Brunekreef EULAR2017 -

Tammo Brunekreef

Mr. Brunekreef observed that a treat to target approach has been recommended for treating early RA, meaning that the aim is to achieve clinical remission signified by a disease activity score in 28 joints (DAS28) score of 2.6 or lower.

“There is no consensus on what the initial treatment should look like, however,” he said. For instance, should remission be induced with methotrexate alone? Or should methotrexate be used in combination with other synthetic disease-modifying antirheumatic drugs (DMARDs)? Or is methotrexate best combined with steroids?

“The early treatment [of RA] is very important because a shorter time to remission is related to sustainability of remission,” Mr. Brunekreef said. “Combination therapy has also been compared in previous studies with methotrexate monotherapy and had been shown to be more effective at 3 and 6 months, although not at 12 months.”

Data on the longer-term follow-up in routine care is lacking, so Mr. Brunekreef and Dutch rheumatologist Hein J. Bernelot Moens, MD, created two historical cohorts of patients with early RA. One cohort of 296 patients had a disease onset between 2006 and 2011 and had received methotrexate monotherapy initiated at 15-20 mg/week. The other cohort of 157 patients had a disease onset between 2012 and 2014 and had been given a combination of oral methotrexate, started at 20 mg/week; oral hydroxychloroquine, started at 200 mg twice daily; and a single 80-120 mg intramuscular injection of triamcinolone that could be repeated after 4 weeks, if necessary.

The mean age of the recruited patients in the monotherapy and combination cohorts was a respective 59.5 and 58.9 years, and 60.5% and 65% were female. More patients in the combination than monotherapy group were rheumatoid factor positive (72.3% vs. 62.2%), with 72.1% and 64.5% being positive for anticitrullinated protein antibodies.

“A number of patients were lost to follow-up due to death (3.7% vs. 1.9%) [or] drug-free remission (1.7% vs. 0.6%) or did not start methotrexate or for other reasons (2.4% vs. 0.6%), but this was not significantly different,” Mr. Brunekreef reported. This left 273 and 124 in each cohort, respectively, who completed 3 years’ of follow-up.

The same percentage of patients in the methotrexate and combination cohorts started a biologic DMARD in the first year (10.8%). A biologic DMARD was recommended if remission was not achieved within 6 months or if there was sustained disease activity after 6 months.

In the second year, however, 6.6% more patients in the methotrexate cohort started a biologic (9.8% vs. 3.2%). Conversely, 1.3% more patients started a biologic in the third year in the combination arm (4% vs. 2.7%). Overall, the receipt of biologics by 21% of monotherapy patients and 14% of combination therapy patients did not differ significantly.

The mean time to the start of the biologic DMARD was similar, however, at around 11-12 months.

Dr. Roy Fleischmann of Dallas EULAR2017 -

Dr. Roy Fleischmann

“It’s an interesting study,” commented Roy Fleischmann, MD, a rheumatologist in group practice in Dallas, during the question and answer session that followed Mr. Brunekreef’s presentation of the data. He queried which version of the DAS28 had been used – DAS28-ESR (erythrocyte sedimentation rate) or DAS28-CRP (C-reactive protein)?

Mr. Brunekreef answered that the DAS28-ESR had been used up to 2015 and then the DAS-CRP from 2016 onward, although the latter was only for patients in year 3, a small number of patients. “We’re looking into a way to translate those data to make them comparable,” Brunekreef said.

“That’s a real problem,” Dr. Fleischmann said, as the DAS28-ESR and DAS28-CRP are not interchangeable. He proposed that these data needed to be looked at using another measure, perhaps the Clinical Disease Activity Index.

Further, Dr. Fleischmann observed that the methotrexate monotherapy data were “absolutely incredible, compared to what we’ve seen in randomized, controlled trials, with 40%-50% of patients in remission.” In clinical trials, about 15% on methotrexate alone achieve an American College of Rheumatology 20 Response Criteria.

“These are very, very strong data, but now I wonder whether or not it’s because of that switch” in DAS28 scoring, Dr. Fleischmann said.

Mr. Brunekreef had no disclosures to report. 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.

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