Biologic DMARD refractory disease quantified in RA patients
medwireNews: At least 6% of patients who have ever received biologic DMARDs for rheumatoid arthritis (RA) will experience refractory disease, suggest UK study findings.
“With increasing treatment options, patients may cycle through several [biologic] DMARDs,” note Kimme Hyrich (University of Manchester) and fellow researchers, highlighting the need for research into the etiopathogenesis of refractory disease given that there “are no current guidelines on optimal [biologic] DMARD sequencing beyond a second [biologic] DMARD.”
The study included 13,502 patients starting first-line tumor necrosis factor (TNF) inhibitor treatment, who were enrolled to the British Society for Rheumatology Biologics Register for RA between 2001 and 2014. The majority (86%) of participants were recruited within the first 8 years.
Over 111,034 person–years of follow-up, 6.4% of patients were classified as having refractory disease, defined as exposure to at least three different classes of biologic DMARD. The median time to refractory disease was 7.9 years.
“This important observation provides information that rheumatologists can use to encourage healthcare providers to address refractory patients,” say Hyrich and team in the Annals of the Rheumatic Diseases.
“Quantifying the frequency of multiple [biologic] DMARD class failure is crucial, particularly in an environment where [biologic] DMARD choice is largely based on custom and experience rather than by individual biomarkers.”
The researchers also point that 6% is likely to be an underestimate because it excludes patients who died, and who persisted with initial therapies or did not switch to another class of DMARD because of comorbidities.
The patients stayed on their first TNF inhibitor for a median of 3.9 years, with most (83%) patients then switching to a B-cell-depleting agent second-line. The main reason for stopping first-line TNF inhibitor treatment was ineffectiveness, followed by adverse events.
Factors independently associated with refractory disease included female sex, younger age, shorter disease duration, poorer global assessment and worse physical function. The researchers also found that patients from lower socioeconomic areas were more likely to develop refractory disease, and modifiable risk factors at the start of treatment such as smoking and obesity played a role.
As expected, more patients recruited early in the study had refractory disease than those recruited later (6.7 vs 4.8%), due to a longer follow-up, but analysis showed that the patients recruited from 2011 onwards were 15 times more likely to have refractory disease than those recruited earlier, after imputation for missing data and adjusting for confounders.
This suggests that the proportion of patients classified as refractory will likely increase over time, say Hyrich et al, who suggest that this could be due to “increased class availability and higher expectations of [biologic] DMARDs.”
The team concludes that “better understanding of [biologic] DMARD refractory disease should help to better target expensive therapies to those patients who are most likely to respond, developing hand in hand with stratified and personalised medicine approaches.”
By Lucy Piper
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