Types of disease modifying antirheumatic drugs:
(1) pharmaceutical disease modifying antirheumatic drugs (DMARDs).
(2) biologic disease modifying antirheumatic drugs (bDMARDs), targeting cytokines or lymphocytes
One definition of refractory disease is resistance to multiple therapeutic drugs with different structures and mechanisms of action (Buch).
A patient who is refractory to bDMARDS typically has progressed through at least 3 classes:
(1) at least one TNF inhibitors
(2) agent targeting B cells
(3) agent targeting IL-6, IL-1 receptor, or T-cell co-stimulation
After each trial of a class there needs to be documentation of persistent inflammation and disease activity. The drug also has to be given for a sufficient period (typically 6 months) and in an adequate dose.
Factors that may contribute to a patient becoming refractory to an agent:
(1) development of antibodies to the targeted therapy
(2) development of toxicity.
Differential diagnosis:
(1) misdiagnosis of rheumatoid arthritis
(2) symptoms coming from a concurrent illness, such as infection
(3) noncompliance
(4) adverse drug effects
