Residual Pain in the Context of Selecting and Switching Biologic Therapy in Inflammatory Rheumatic Diseases

Abstract

For many years, inflammatory rheumatic diseases (IRDs) represented a source of disappointment in medical care caused by the mediocre efficacy of the available treatments. Some of these diseases, like Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS), caused fear in the general population, especially due to associated joint deformities and subsequent disabilities. However, in the last 20 years, a new successful class of antirheumatic drugs has become available: biologic Disease-Modifying Antirheumatic Drugs (bDMARDs). Due to this innovative treatment, the days are over when joint and spine deformities defined the condition of a person with RA or AS. Nonetheless, expectations are higher today, and other clinical problems, (not entirely solved by bDMARDs), seem to drive the drug selection during the span of rheumatic diseases. Most of these issues are covered by the term "unmet needs." One of the most intriguing of such needs is the residual pain (RP) in patients that are otherwise in the biological remission of the disease. Present in a significant proportion of the patients that enter remission status, RP is poorly understood and managed. In recent years, new data has become available in this area and new conceptual clarifications have occurred. In this review, we explain the various nature of RP and the necessity of treatment diversification in such situations. All in all, we believe this condition is far more complex than simple pain and includes other clinical aspects, too (like fatigue or mood changes) so the terms Post-Remission Syndrome (PRS), and PRS pain might be more appropriate.

Keywords: ankilosing spondylitis; biologic therapy; disease modifying anti-rhuematic drugs; post remission syndrome; remission; residual pain; rheumatod arthritis; switch.

Figure 1

Relation between pain type and sensory neurons functionality. (A) Normal sensory neuron without any stimulus. (B) Nociplastic pain situation: a normal sensory neuron surrounded by a hostile microenvironment is receiving a subliminal stimulus. (C) Nociceptive pain situation: a normal sensory neuron receives a proper magnitude stimulation. (D) Neuropathic pain situation: an injured sensory neuron does not receive any stimulation of the receptors, or the stimuli are insignificant. In (B–D) situations the result is similar: an electrical impulse (orange arrowheads) is created. R, receptor; CB, cellular body; S, stimulus; L, the lesioned area of the sensory neuron.

Figure 2

Different scenarios of RP in IRDs. (A) No RP (pain after remission <20 mm VAS). (B) RP is the unresolved part of the pain generated by inflammatory rheumatic disease (IRD). (C) RP comes from a second source developed during the evolution of the rheumatic disease and independent of the pain generated by IRD. (D) RP comes from a second source with the onset that preceded the onset of IRD; this source does not end after the remission of IRD.