Features of clinical manifestations of rheumatoid arthritis in patients after failure of conventional synthetic disease-modifying antirheumatic drugs therapy depending on the signs of central sensitization

Abstract

Central sensitization (CS) is a condition characterised by (associated with) neuroplastic changes in nociceptive neurons, sub-threshold afferent input, pain hypersensitivity and development widespread pain. Insufficient response to disease-modifying antirheumatic drugs (DMARDs) can be caused by CS.Objective – to evaluate the features of clinical manifestations of RA in patients with ineffective antirheumatic therapy, depending on the presence of signs of CS.Material and methods. The study group included 509 patients diagnosed with RA (according to ACR/EULAR classification criteria, 2010) with moderate or high disease activity (DAS28-CRP≥3.2) and ineffectiveness or intolerance of conventional synthetic DMARDs, biological DMARDs and JAK inhibitors. Disease activity in patient with RA was assessed by DAS28-CRP. Our study did not include an examination by a neurologist to detect signs of CS, so the Central Sensitization Inventory (CSI) (part one) was used. The BPI questionnaire was used for assessing clinical pain intensity. The PainDETECT, FSS, FIRST, HAQ questionnaires were used for screening neuropathic pain symptoms (NPS), fatigue, fibromyalgia signs and functional impairment, respectively. The HADS questionnaire was recommended for early diagnosis anxiety and depression disorders.Results. Signs of CS (CSI≥40), with a median of 42 [32; 53], were found in 57.2% of the examined patient. Patients with signs of CS were established to have poorer health measure (PGA – 64.6±13.5 and 53.5±16.8; p=0.001), higher pain intensity in all BPI scales, longer morning stiffness – 90 [30; 180] and 60 [20; 120] minutes (p=0.001), more painful joints – 8 [5; 12] and 7 [4; 10] (p=0.005), worse functional status in HAQ (1.65±0.7 and 1.08±0.5; p=0.001) and higher disease activity in DAS28-CRP (4.9±1.0 and 4.6±0.9; p=0.001) compared to patients without signs of CS. There was also direct correlation between CS and a high frequency of having an NPS (PainDETECT>18) – 34.5% and 10.3% (p=0.001), significant anxiety and depression (HADS>11) – 29,0% and 5.1% (p=0.001) and 26.3% and 4.2% (p=0.001) respectively, fatigue (FSS) – 96.5% and 70.4% (p=0.001), signs of fibromyalgia (FIRST≥5) – 38.4% and 6.1% (p=0.001).Conclusion. The presence of signs of CS in patient with RA significantly enhance many symptoms of disease, being associated with higher pain intensity, fatigue, impaired function, higher incidence of NPS, depression and anxiety, and fibromyalgia.