DMARD-Based Strategies Provide Clinically Relevant Pain Relief in RA and PsA

Intensive treatments, including synthetic, biologic, or targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid (RA) and psoriatic arthritis (PsA) help control pain and should be complemented by bespoke pain management strategies.1

“Understanding the impact of intensive management on pain in patients with inflammatory arthritis is important. If it improves patients’ pain from perspectives which matter to them – achieving mild pain levels and substantial pain reductions – this would support moving the focus of pain care from prescribing opioids towards conventional DMARDs and other treatments of proven efficacy. We addressed this evidence gap in secondary analyses of three randomized controlled trials (RCTs) evaluating the impact of varying levels of intensive management on pain intensity outcomes from a range of different perspectives in patients with RA and PsA,” lead investigator Fowzia Ibrahim Centre for Rheumatic Diseases, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London Cutcombe Road, London, United Kingdom, and colleagues wrote.1

Ibrahim and colleagues analyzed data from the MIPA (PsA), CARDERA (early RA), and TITRATE (established RA) trials. The trials measured pain using a 100-mm pain intensity visual analogue scale (VAS). They evaluated the impact of intensive treatment on achieving “mild” endpoint pain intensity scores (of ≤ 34), mean changes in pain intensity scores, and achieving at least 30% reductions in pain intensity scores using t-tests, chi-squared tests, and adjusted regression models. Intensive treatment was defined as using combination DMARDs or undertaking regular assessments with the application of treat-to-target principle.

The analysis included 128 participants from MIPA, 379 from CARDERA, and 258 from TITRATE that had endpoint outcome data available. The investigators found that overall, significantly more patients achieved mild endpoint pain intensity scores with intensive compared to control treatment (MIPA [70% vs. 42%; P = .003]; CARDERA [71% vs. 56%; P = .011]; TITRATE [67% vs. 50%; P = .008]).1

CARDERA and TITRATE employed the most intensive management strategies and Ibrahim and colleagues found that overall reductions in pain scores were significantly greater (6.6-6.8 units in adjusted linear regression models), and significantly more participants achieved at least 30% reductions in pain with intensive compared to control treatment (CARDERA odds ratio [OR], 1.9; P = .009; TITRATE OR 2.2; P = .002).1

“We conclude that, across a range of trial designs and settings, there is good evidence that intensive management using DMARDs improves pain intensity in patients with active RA and PsA over 6 months or longer in a manner that is clinically relevant to them. This contrasts with the limited evidence for opioid efficacy in short-term historical trials. Our analysis supports EULAR guidance that optimizing disease activity is crucial for pain control,” Ibrahim and colleagues concluded.1

Other recent research into pain and rheumatoid disease found that metabolic syndrome (MetS) is highly prevalent and associated with increased levels of pain catastrophizing in patients with PsA.2 Investigators observed a Pain Catastrophizing Scale (PCS) median value of 18 (range, 6–32). Regarding its domains, the helplessness median value was 7 (range, 2–14), the rumination median value was 7 (range, 2–13.5), and the magnification median value was 3 (range, 1–5).2

Univariable analysis revealed a positive association between PCS and female sex (b = 8.61; 95% CI, 4.02-13.2; P <.001), DAPSA values (b = 0.78; 95% CI, 0.58-0.97; P <.001), diagnosis of fibromyalgia (b = 12.24; 95% CI, 8-16.48; P <.001), and presence of MetS (b = 13.96; 95% CI, 9.94-17.98; P <.001). After adjusting for age, sex, fibromyalgia, and DAPSA disease activity, multivariable linear regression analysis showed a significant association between PCS and MetS (b = 8.84; 95% CI, 4.66-13.02; P <.0001), and between PCS and DAPSA (b = 0.55; 95% CI, 0.34-0.77; P <.0001).2

“Interventions targeting both metabolic health and psychological well-being, such as lifestyle modifications, pharmacological treatments, and cognitive-behavioral therapy, could potentially improve the management of patients with PsA affected by MetS,” lead investigator Damiano Currado, MD, an immune-rheumatology specialist at Campus Bio-Medico University Hospital Foundation in Rome, and colleagues wrote.2

REFERENCES

1. Ibrahim F, Scott DL, Scott IC. The impact of intensive management on pain intensity in patients with rheumatoid arthritis and psoriatic arthritis: secondary analysis of three clinical trials. BMC Rheumatol. 2025;9(1):55. Published 2025 May 21. doi:10.1186/s41927-025-00493-z

2. Currado D, Berardicurti O, Saracino F, et al. The Relationship Between Metabolic Syndrome and Pain Catastrophizing in Psoriatic Arthritis. Rheumatol Ther (2025). https://doi.org/10.1007/s40744-025-00758-6