medwireNews: Several studies presented at the 2017 ACR/ARHP Annual Meeting in San Diego, California, USA, explored different aspects of rheumatoid arthritis (RA) treatment, including guideline recommendations, adherence to second-line therapy, and predicting treatment response.
Optimizing methotrexate use
Vivian Bykerk, from Mount Sinai Hospital in Toronto, Ontario, Canada, presented the results of a study of 2227 patients from the Canadian Early Inflammatory Arthritis Cohort showing that guideline recommendations emphasizing optimal early methotrexate use have largely been followed in Canada.
The researchers compared RA treatment strategies during the time periods before and after the guidelines were issued in 2011, and found that patients were more likely to undergo early transition to higher (≥20 mg) doses of methotrexate in 2011–2016 than they were in 2007–2010. There was also a 10% increase in the use of subcutaneous compared with oral methotrexate in the later period, and patients were significantly more likely to undergo rapid escalation to biologic therapies after 2011.
In accordance with these results, a significantly higher proportion of patients were in remission, according to the Clinical Disease Activity Index (CDAI) definition, in 2011–2016 compared with the earlier period.
These findings suggest that recommendations for optimal use of methotrexate “were reflected in the recent time period,” said Bykerk.
However, she noted that 25–30% of patients did not achieve low disease activity or remission after 12 months of treatment, highlighting “a gap in care and an unmet need that needs to be overcome.”
The following presentation focused on adherence to methotrexate in the USA. In an analysis of 2144 patients who initiated methotrexate treatment in the Corrona registry, Jeffrey Curtis (University of Alabama at Birmingham, USA) and colleagues found that 24% of patients discontinued monotherapy within 1 year, 37% discontinued treatment at 2 years, and 46% had stopped by the 3-year follow-up. Age at onset, disease duration, and baseline CDAI were identified as significant predictors of treatment discontinuation.
“We need better strategies to both identify patients with suboptimal [adherence to methotrexate], and to predict or at least to recognize those who are not tolerating methotrexate […] so that we can get them on the best and most effective care,” concluded Curtis.
Choosing second-line biologics and predicting treatment response
In his presentation, Denis Choquette, from the Institut de Recherche en Rhumatologie de Montréal in Quebec, Canada, focused on treatment adherence after switching from one biologic agent to another.
Until approximately 10 years ago, tumor necrosis factor (TNF) inhibitors were the only biologic agents available for RA, and rheumatologists switched between different TNF inhibitors if one agent failed, but biologic agents with different mechanisms of action – including abatacept and rituximab – have since become available, explained Choquette.
Using the Rhumadata registry to compare long-term adherence after switching to second-line biologic treatment, the researchers found that 76.7% of 92 patients remained on second-line abatacept therapy 1 year after switching from a TNF inhibitor, compared with 50.5% of the 194 patients who switched to another TNF inhibitor.
Patients remained on treatment for a mean of 3.3 years and 2.71 years, respectively, and treatment retention rates were significantly higher among those in the second-line abatacept group, said Choquette. He explained that lack of efficacy and occurrence of adverse events were the most common reasons for treatment discontinuation.
And he concluded that “abatacept shows better sustainability over a second-line anti-TNF in patients with RA who have failed one prior [biologic] DMARD.”
Also focusing on treatment with abatacept and TNF inhibitors, Sean Connolly (Bristol-Myers Squibb Inc, Princeton, New Jersey, USA) described two models to predict treatment response that were generated using baseline data from the AMPLE study, a phase III trial comparing abatacept and adalimumab for the treatment of moderate-to-severe, biologic-naïve RA.
The models took demographics, baseline biomarkers, and disease activity measures into account. Treatment responders were defined as those who achieved at least a 70% improvement in ACR criteria after 1 year of treatment, while patients who failed to achieve at least a 20% improvement were categorized as nonresponders.
The abatacept and adalimumab models correctly distinguished between patients who did and did not respond to treatment on 85.5% and 86.0% of occasions, respectively. Furthermore, the abatacept model failed to identify patients who responded to adalimumab, and vice versa.
Connolly cautioned that these findings require independent validation, but believes that predictive models using readily available variables from large head-to-head trials could help to find “the right drug for the right patient at the right time.”
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