UK researchers have developed what they say is the first model to identify patients who will not respond to methotrexate based on ‘real world data’.

The model has flagged anxiety as a significant overlooked predictor of non-response to the conventional DMARD within six months of starting treatment.

Writing in Arthritis Research & Therapy, the researchers from the Arthritis Research UK Centre for Epidemiology at Manchester University say that previous methotrexate non-response prediction models have been based on small, unrepresentative numbers of patients from clinical trials.

In their study they analysed data from 1050 patients recruited to the Rheumatoid Arthritis Medication Study (RAMS), an observational study of patients starting methotrexate for the first time.

They defined non-response at six months based on EULAR criteria, discontinuation due to inefficacy or starting biologic therapy.

Overall, 43% of patients were classed as non-responders, with five factors being independent predictors of non-response:

• Rheumatoid  Factor negativity.
• Higher functionality (Health Assessment Questionnaire) score.
• Higher tender joint count.
• Higher (Hospital Anxiety and Depression Scale) anxiety score.
• Lower disease activity.

The researchers said the model was the first to be developed form a large cohort of patients starting methotrexate in routine clinical care, similar to the real world setting in which it might be applied.

They suggest it could be used in clinical practice to identify which patients could be considered for early access to additional medications to control RA. However, a key issue was the threshold for labelling patients at high risk of non-response.

Using a predicted probability of 0.9 would identify patients who were all at high risk of non-response but would only capture 4% of all non-responders.

Lowering the threshold would identify more non-responders but at the expense of labelling some at high risk who actually respond to methotrexate, they noted.

“It might be reasonable to consider by-passing MTX therapy altogether in patients predicted to be very unlikely to respond,” they suggest.

“Would it be reasonable to accept a lower probability of non-response as a guide to MTX prescription – or a guide to starting combination therapy? This depends to some extent on the alternative forms of treatment and their efficacy in individuals predicted not to respond to MTX, and their cost.

They conclude that it would be reasonable to continue to prescribe MTX for most patients in whom it is not contra-indicated but with a low threshold to move on to stronger combination or biological therapy if there is non-response at 6 months.