Pain Centralization Associated With Response to DMARD Therapy in Rheumatoid Arthritis

Unrecognizable man with pain in his hand talks with an unrecognizable female doctor.
Researchers assessed the association between dysregulated central pain processing and treatment response in rheumatoid arthritis.

Dysregulation of pain centralization is significantly associated with poor response to disease-modifying antirheumatic drug (DMARD) therapy in patients with rheumatoid arthritis (RA), according to study results published in Arthritis & Rheumatology.

Evidence suggests that patients with RA show abnormal patterns of pain centralization. Using data from the Central Pain in RA (CPIRA) cohort, investigators aimed to determine whether baseline pain centralization was predictive of response to DMARD therapy.

Before initiating DMARD therapy, patients received quantitative sensory testing, which included assessment of pressure pain detection thresholds at the trapezius muscles, temporal summation (TS), and conditioned pain modulation (CPM). Disease activity was measured using the 28 joint count Disease Activity Score C-reactive protein (DAS28-CRP). Treatment response was defined by the European League Against Rheumatism (EULAR) response criteria, according to which a good treatment response was DAS28-CRP ≤3.2 at 12 weeks and a change in DAS28-CRP from a baseline of >1.2; a moderate response was any improvement that did not meet the criteria for a good response.

A total of 182 patients (83.0% women) were included in the analysis with mean baseline DAS28-CRP of 4.3. At 12 weeks, 28.6% of patients had a good and 32.4% had a moderate EULAR response. No treatment response was observed for 39.0% of participants. Researchers observed a good treatment response in 22.5% of patients with high CPM dysregulation, compared with 40.3% in those with low CPM dysregulation (P =.01). Patients with high vs low CPM dysregulation were significantly less likely to achieve a good treatment response (odds ratio [OR], 0.40; 95% CI, 0.19-0.83). This association was primarily driven by differences in the tender joint count, which decreased by an average 3.52 and 6.29 in the high and low CPM dysregulation groups, respectively. Similar results were observed for study participants with high dysregulation of pressure pain thresholds and TS, but these associations were not significant.

In the secondary analysis, the percentage of participants who achieved a good treatment response was highest in those with low CPM and TS dysregulation (52.6%) and lowest in those with high CPM and TS dysregulation (21.8%). Compared with low TS and CPM dysregulation, both CPM and TS was associated with a lower likelihood of achieving a good EULAR response (OR, 0.23; 95% CI, 0.07-0.73).

Investigators noted that the interpretation of dysregulation may be limited, as a control group of healthy individuals was not included for comparison.

“These findings indicate a role for pain centralization in DMARD response in RA,” the researchers concluded. “Recognition of pain centralization as a contributor to disease presentation could facilitate optimizing a patient’s medication regimen without escalating DMARD therapy, which is accompanied by inherent risks.”

Disclosures: Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Heisler AC, Song J, Muhammad LN, et al. Association of dysregulated central pain processing and response to disease-modifying anti-rheumatic drug therapy in rheumatoid arthritis [published online July 19, 2020]. Arthritis Rheumatol. doi:10.1002/art.41440