Tor Olofsson1, Johan K Wallman1, Anna Jöud2, Maria E C Schelin2, Sofia Ernestam3, Ronald van Vollenhoven4, Saedis Saevarsdottir5, Jon Lampa4. 1. Lund University, Skåne University Hospital, Lund, Sweden. 2. Lund University, Lund, Sweden. 3. Academic Specialist Centre, Stockholm Health Services and Karolinska Institutet, Stockholm, Sweden. 4. Karolinska Institutet, Stockholm, Sweden. 5. Karolinska Institutet, Stockholm, Sweden, and University of Iceland and deCODE genetics, Reykjavik, Iceland.
Abstract
OBJECTIVE: To compare the pain course between methotrexate (MTX)-refractory early rheumatoid arthritis (RA) patients randomized to infliximab (IFX) versus sulfasalazine (SSZ) plus hydroxychloroquine (HCQ). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
RCT Entities:
OBJECTIVE: To compare the pain course between methotrexate (MTX)-refractory early rheumatoid arthritis (RA) patients randomized to infliximab (IFX) versus sulfasalazine (SSZ) plus hydroxychloroquine (HCQ). METHODS: The randomized, controlled, open-label Swedish Pharmacotherapy (SWEFOT) trial enrolled new-onset RApatients 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. RESULTS: 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. CONCLUSION: Despite active combination treatment, almost one-third of new-onset RApatients 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.
Authors: Alvaro Gomez; Victor Qiu; Arvid Cederlund; Alexander Borg; Julius Lindblom; Sharzad Emamikia; Yvonne Enman; Jon Lampa; Ioannis Parodis Journal: Front Med (Lausanne) Date: 2021-04-16