The concept of difficult-to-treat disease in rheumatology: where next?

New pathogenesis-based therapeutics and evidence-based consensus treatment recommendations, often with predefined treatment goals, have remarkably improved outcomes across many chronic diseases. However, a clinically significant subgroup of patients responds poorly to interventions and show a progressive decline in the disease trajectory, which poses an increasing health-care challenge. Difficult-to-treat approaches exist in several areas of medicine and the need for similar definitions has recently also emerged in rheumatology. The term difficult-to-treat refers not only to patients with pathology-driven, treatment-refractory disease, but also implicates multiple other factors that can contribute to patients being in this state, including having few treatment options, misdiagnosis, and coincident psychosocial factors. Therefore, the difficult-to-treat state requires a comprehensive, holistic, multidisciplinary approach that considers the specific characteristics of each disease and the personalised needs of the patient. In this Personal View, we provide an overview of the different aspects of the concept of difficult-to-treat disease, highlight its advantages, and propose the importance of incorporating this concept more widely in the design of rheumatological treatment strategies.