The efficacy of systemic glucocorticosteroids for pain in rheumatoid arthritis: a systematic literature review and meta-analysis

Abstract

Objectives Glucocorticosteroids (GCs) are recommended to suppress inflammation in people with active RA. This systematic review and meta-analysis aimed to quantify the effects of systemic GCs on RA pain. Methods A systematic literature review of randomised controlled trials (RCTs) in RA comparing systemic GCs to inactive treatment. Three databases were and spontaneous pain and evoked pain outcomes were extracted. Standardized mean differences (SMDs) and mean differences (MDs) were meta-analysed. Heterogeneity (I2, tau statistics) and bias (funnel plot, Eggers test) were assessed. Subgroup analyses investigated sources of variation. This study was pre-registered (PROSPERO CRD42019111562). Results 18903 titles, 880 abstracts and 226 full texts were assessed. Thirty three RCTs suitable for the meta-analysis included 2658 participants. Pain scores (spontaneous pain) decreased in participants treated with oral GCs; SMD= -0.65 (15 studies, 95% CI, -0.82, -0.49, p< 0.001) with significant heterogeneity (I2=56%, p= 0.0002). Efficacy displayed time-related decreases after GC initiation. Mean difference VAS pain was -12mm (95% CI, -14mm to -9mm) greater improvement in GC than control at ≤ 3 months, -8mm (95% CI, -12mm, -3mm) at > 3–6 months, and -6mm (95% CI, -10mm, -2mm) at > 6 months. Similar findings were obtained when evoked pain outcomes were examined. Data from 5 RCTs suggested improvement also in fatigue during GC treatment. Conclusion Oral GCs are analgesic in RA. The benefit is greatest shortly after initiation and GCs might not achieve clinically important pain relief beyond 3 months. Treatments other than anti-inflammatory GCs should be considered to reduce the long-term burden of pain in RA.

The Role of Autophagy as a Trigger of Post-Translational Modifications of Proteins and Extracellular Vesicles in the Pathogenesis of Rheumatoid Arthritis

“…[ 15,17] Conventional synthetic DMARDs (i.e., Methotrexate (MTX), Hydroxychloroquine (HCQ), Sulfasalazine, Leflunomide, Azathioprine)…”

“…However, synovial histological and transcriptional analyses have shown marked heterogeneity among patients with established RA; therefore, approaches based on systems biology might also help in patient stratification according to the different pathogenic pathways for treatment personalization [ 14 ]. Therefore, drugs that interfere with the previous pathogenic mechanisms have been shown to be useful in the treatment of RA patients [ 9 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] ( Table 1 ).…”

Spontaneous pain as a challenge of research and management in chronic pain

“…Pharmacological treatments remain the traditional management of spontaneous pain. Glucocorticosteroids are recommended to suppress inflammation and relieve spontaneous pain in patients with active rheumatoid arthritis [ 95 ]. The neuronal hyperexcitability and corresponding molecular changes in neuropathic pain have many features in common with the cellular changes in certain forms of epilepsy, which leads to the use of anticonvulsant drugs for treating spontaneous pain [ 96 ].…”

CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier

“…Steroids, which are either derived from dietary sources or synthesized within the body, are defined by their distinctive four-ring carbon structure and play vital roles as hormones in various physiological functions. These compounds have been employed in numerous therapeutic applications for a broad array of human disorders [ 38 , 39 , 40 ], such as vascular conditions, although their use continues to be a subject of debate [ 41 ]. Specifically, the importance of progesterone (PRG), a key female sex steroid, in preserving the integrity of the blood–brain barrier has been the focus of extensive research.…”