Residual pain and fatigue are affected by disease perception in rheumatoid arthritis in sustained clinical and ultrasound remission

Abstract

Objective: Regardless of remission status, residual pain (RP) might persist in rheumatoid arthritis (RA). The aim of this study was to characterize RP, its perception, and patient-dependent features and to evaluate its possible association with residual synovitis in patients with RA in remission.

Methods: Ninety-seven patients with RA, including 68 in sustained clinical and ultrasound remission (Rem/RA) and 29 in high/moderate DAS28-CRP disease activity (H-Mo/RA) were enrolled in the study. Thirty patients with fibromyalgia were enrolled as a control group(FIBRO). At study entry, demographic, clinical, ultrasound characteristics, and pain dimension assessment (VAS-pain, FACIT, CSI, GHQ, and RAID) were collected for each patient. RA patients underwent synovial tissue biopsy to evaluate the degree of synovitis using the Krenn synovitis score (KSS).

Results: Forty-eight percent of Rem/RA still declared unacceptable pain (VAS-Pain > 20) compared to 80% of H-Mo/RA patients (p < 0.0001). Furthermore, Rem/RA patients presented comparable levels of pain dimension assessment regardless of KSS. However, classifying Rem/RA group based on RAID score (< 2 as satisfied SAT-Rem/RA and ≥ 2 as unsatisfied UNSAT-Rem/RA), SAT-Rem/RA group presented a lower grade of VAS-Pain (p < 0.0001), lower percentage of patients with an unacceptable pain (p < 0.0001) and lower grade of fatigue(p < 0.0001) compared to the UNSAT-Rem/RA patients. The percentage of SAT-Rem/RA patients who presented a disease flare did not differ from UNSAT-Rem/RA over the 24 months of follow-up. Finally, female Rem/RA patients presented higher VAS-Pain compared to male Rem/RA (p = 0.0119).

Conclusions: Moreover,73% satisfied female Rem/Ra patients presented an acceptable pain compared to 23% unsatisfied female Rem/RA patients (p = 0.001). RP in RA patients in remission can represent the way by which the patients communicate their state of non-acceptance of the disease. It can be useful to treat RP with the appropriate treatments. Key Points • Rheumatoid arthritis patients still reported unacceptable residual pain despite sustained clinical and ultrasound remission and despite the low grade/absence of histological synovitis. • Only a small rate of rheumatoid arthritis patients in sustained clinical and ultrasound remission showed residual pain as part of a central sensitivity syndrome or psychiatric disorders. • Rheumatoid arthritis patients in sustained clinical and ultrasound remission complained residual pain and fatigue as part of not acceptance of disease and/or dissatisfaction in the disease management.

Keywords: Pain; Patient-reported outcomes; Remission; Rheumatoid arthritis.

Fig. 1

Pain assessment in RA patients across disease stages and fibromyalgia patients. a, b VAS-Pain and FACIT scores in RA patients stratified by disease stage namely DAS28-CRP based remission (Rem/RA) and DAS28-CRP based high-moderate disease activity (H-Mo/RA) and fibromyalgia patients (FIBRO). ANOVA test and Mann–Whitney test were used. Every dot is a patient. The median is shown as a blank line in the box, interquartile range is delimited by the box. p-value ≤ 0.05 was considered statistically significant. The dotted red line indicates VAS-Pain > 20 as threshold unacceptable pain; c rate of unacceptable pain in Rem/RA vs H-Mo/RA patients in the enrolled cohort. The chi-square test was used. p-value ≤ 0.05 was considered statistically significant

Fig. 2

RAID score in RA in different clinical stages. a RAID score in Rem/RA, H-Mo/RA, and FIBRO groups. ANOVA test and Mann–Whitney test were used. Every dot is a patient. The median is shown as a blank line in the box, interquartile range is delimited by the box. The blue dotted line indicates the RAID cutoff of 2. p-value ≤ 0.05 was considered statistically significant. b Rate of patient-acceptable symptom state (RAID cutoff = 2) in Rem/RA and H-Mo/RA. The chi-square test was used. p-value ≤ 0.05 was considered statistically significant. FIBRO, fibromyalgia patients; Rem/RA, rheumatoid arthritis patients in DAS28-CRP-based remission; H-Mo/RA, rheumatoid arthritis patients in DAS28-CRP based high/moderate disease activity

Fig. 3

Residual pain and rates of patient dissatisfaction in RA in remission. a VAS-Pain score in Rem/RA with RAID < 2 (SAT), Rem/RA with RAID ≥ 2 (UNSAT), or H-Mo/RA groups. ANOVA test and Mann–Whitney test were used. Every dot is a patient. The median is shown as a blank line in the box, interquartile range is delimited by the box. The dotted orange line indicates the VAS-Pain cutoff of 20. b Rate of unacceptable pain in Rem/RA based on their RAID score (RAID < 2 (SAT), Rem/RA with RAID ≥ 2(UNSAT)). c FACIT score in Rem/RA with RAID < 2 (SAT), Rem/RA with RAID ≥ 2 (UNSAT), or H-Mo/RA groups. ANOVA test and Mann–Whitney test were used. Every dot is a patient. The median is shown as a blank line in the box, interquartile range is delimited by the box. p-value ≤ 0.05 was considered statistically significant. Rem/RA, rheumatoid arthritis patients in DAS28-CRP-based remission; H-Mo/RA, rheumatoid arthritis patients in DAS28-CRP-based high/moderate disease activity

Fig. 4

Residual pain is associated with the female sex in a remission state. a VAS-Pain score in Rem/RA and H-Mo/RA stratified based on sex. Mann–Whitney test was used. Every dot is a patient. The median is shown as a blank line in the box; the interquartile range is delimited by the box. The orange dotted line indicates the VAS-Pain cutoff = 20. b VAS-Pain score in female Rem/RA (Rem/fRA) stratified based on RAID < 2 (SAT), Rem/RA with RAID ≥ 2 (UNSAT), and female H-Mo/RA (H-Mo/fRA) groups. ANOVA and Mann–Whitney test were used. Every dot is a patient. The median is shown as a blank line in the box; the interquartile range is delimited by the box. The orange dotted line indicates the VAS-Pain cutoff = 20. c Rate of unacceptable pain in female Rem/RA (Rem/fRA) based on their RAID score (RAID < 2 (SAT) and Rem/RA with RAID ≥ 2 (UNSAT) respectively). The chi-square test was used. Rem/RA, rheumatoid arthritis patients in DAS28-CRP-based remission; H-Mo/RA, rheumatoid arthritis patients in DAS28-CRP-based high/moderate disease activity