To compare the pain course between methotrexate (MTX)-refractory early rheumatoid arthritis (RA) patients randomized to infliximab (IFX) versus sulfasalazine (SSZ) plus hydroxychloroquine (HCQ).
The randomized, controlled, open-label Swedish Pharmacotherapy (SWEFOT) trial enrolled new-onset RA patients from October 2002 to December 2005. After 3 months of receiving MTX, patients not reaching low disease activity (Disease Activity Score in 28 joints score ≤3.2) were randomized to adding IFX (n = 128) or SSZ plus HCQ (n = 130) and followed for 21 months. Here, outcomes included area under the curve (AUC) for visual analog scale (VAS) scores for pain, unacceptable pain (VAS pain score >40 mm [range 0-100]), and unacceptable pain despite inflammation control (refractory pain; VAS pain score >40 plus C-reactive protein level <10 mg/liter). Between-group differences were analyzed with multivariate regression models.
Overall, 50% of randomized patients (n = 258) in the crude setting reported unacceptable pain at randomization, declining to 29% at 21 months (P < 0.001), when refractory pain constituted 82% of all unacceptable pain. Comparing randomized arms (intent-to-treat analysis), the AUC for VAS pain was lower in the MTX plus IFX group (P = 0.01), and at 21 months, 32% of patients receiving MTX plus IFX and 45% receiving MTX plus SSZ plus HCQ had unacceptable pain (adjusted relative risk 0.68 [95% confidence interval 0.51, 0.90]; P = 0.008). Regarding refractory pain, no between-group differences were observed.
Despite active combination treatment, almost one-third of new-onset RA patients reported unacceptable pain after 21 months, and refractory pain constituted more than 4/5 of this pain load. Adding IFX versus SSZ plus HCQ to MTX reduced both cumulative pain and unacceptable pain at 21 months, suggesting less long-term pain for the biologic therapy. These results display insufficient effects of current treatment strategies on inflammation-independent pain components, warranting alternative approaches in affected patients.