Targeting contributory factors in difficult-to-treat rheumatoid arthritis

Despite recent advances with the introduction of biologic/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs); there is a growing number of individuals with rheumatoid arthritis (RA) in whom stepwise escalation of current treatment modalities remain ineffective1. Improvement in disease activity can be impacted by inflammatory and non-inflammatory components, and thus improving outcomes in this cohort of patients relies on holistic care. Recently, the European Alliance of Associations for Rheumatology (EULAR) defined this subset of RA patients as 'Difficult-to-treat' (D2T-RA), whereby there is failure of ≥2 b/tsDMARDs classes with signs/symptoms of disease activity or burden2. D2T-RA represents a significant area of clinical unmet need in the NHS, consisting of individuals with complex needs. Herein, we looked at identifying the presence of non-inflammatory aspects of D2T-RA in a real-world cohort; with the objective of providing justification for the development of a novel multidisciplinary clinic through which we can approach and address the needs of patients with D2T-RA. RA patients aged ≥18 who had failed two or more classes of b/tsDMARDs were identified and recruited from two centres. Clinical, demographic, and serological data were collected at baseline. Responses were collected to questionnaires including: fulfilment of fibromyalgia classification criteria, Patient Health Questionnaire-9 (PHQ-9), Brief Illness Perception Questionnaire (B-IPQ), Beliefs about Medicines Questionnaire-Specific (BMQ-S), fatigue visual analogue scores (VAS) and Medication Adherence Report Scale-5 (MARS-5). A total of 19 patients fulfilling EULAR defined D2T-RA criteria were recruited. Patient, disease and outcome characteristics are summarised in Table 1. In brief, 90% were female and 90% were anti-CCP positive. Median BMI was raised at 25.8, and median disease activity scores reflected moderate disease. Four patients were classified as having co-existing fibromyalgia. Median PHQ-9 and VAS scores reflect a mild level of depressive illness and high level of self-reported fatigue respectively. Ever-non adherence (classified as a response other than 'never' within the MARS-5 questionnaire) was noted in 47% and 37% of the cohort in regards to csDMARDs and b/tsDMARDS respectively - despite an overall accepting view of treatment based on the positive necessity-concerns differential (NCD). In conjunction with advances in biologic therapies, treatment stratification and early intervention; management of non-inflammatory factors is likely to provide benefit to the D2T-RA cohort. Our results show that factors such as increased BMI, depression, fatigue, non-adherence, fibromyalgia, and a negative view of illness are present in a population of D2T-RA patients. These can impact on treatment response and patient outcomes. The creation of a dedicated, robust, multi-disciplinary clinic, aimed at identification, targeted management and follow-up of these potentially modifiable factors could prove valuable in managing this complex group of patients.