From the Journals

Unacceptable RA pain may drop with TNFi treatment but still lingers in many patients



Unacceptable pain more often remains among patients with early, methotrexate-refractory (RA who move on to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine than biologic combination therapy with the tumor necrosis factor inhibitor infliximab (Remicade) plus methotrexate, according to findings from 21 months of follow-up in a post hoc analysis of data from the randomized, controlled Swedish Farmacotherapy (SWEFOT) trial.

Dr. Tor Olofsson of Lund University

Dr. Tor Olofsson

Although RA patients who took biologic combination therapy had 32% lower risk for unacceptable pain (rated at >40 mm on a 0- to 100-mm visual analog scale) at 21 months, they still had no difference from patients taking triple therapy in the rate of pain described as refractory, or unacceptable despite inflammation control (C-reactive protein <10 mg/L).

While these results lend “some support to a better effect on long-term pain for the biological treatment, compared with triple therapy ... our findings are also in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain components, warranting early alternative treatment approaches in affected patients,” Tor Olofsson, MD, PhD, of Lund (Sweden) University, and colleagues wrote in Arthritis Care & Research.

The pain outcomes analyzed in this post hoc study were all secondary outcomes of the original open-label SWEFOT trial, which during 2002-2005 enrolled 258 RA patients with less than a year of symptoms who did not reach low disease activity (28-joint Disease Activity Score ≤3.2) after 3 months of methotrexate and randomized them to an addition of either infliximab (3 mg/kg rounded up to nearest 100-mg increment) or sulfasalazine 1,000 mg twice daily plus hydroxychloroquine 400 mg once daily.

Overall, 90 of 128 patients in the infliximab group and 74 of 130 in the triple-therapy group continued the protocol until the 21-month follow-up. Patients in the infliximab group had a significantly lower area under the curve for visual analog scale for pain, most of which was accounted for during months 9-21. The percentage of patients in the infliximab group with unacceptable pain also dropped significantly from 57% at randomization to 32% at 21 months, while no difference was seen for triple therapy patients, of whom 45% had unacceptable pain at 21 months.

While patients in the infliximab group had a significantly lower risk of unacceptable pain without inflammatory control at 21 months, neither treatment arm showed a within-group difference in refractory pain from randomization to the 21-month follow-up.

Nearly one-third of patients overall still reported unacceptable pain 21 months after addition of either infliximab or sulfasalazine plus hydroxychloroquine. And at that time point, refractory pain constituted 82% of all unacceptable pain. “Notably, this pattern – with a domination of refractory pain – was evident already 3 months after starting combination therapy,” Dr. Olofsson and colleagues wrote.

The original SWEFOT study was supported in part by a grant from the Swedish Rheumatism Association, and in part by an annual unrestricted grant from Schering-Plough Sweden (now Merck Sharp & Dohme). The post hoc analysis was supported by Lund University and the Kockska Foundation, the Swedish Research Council, and the Stockholm County Council. Two authors disclosed financial relationships with multiple pharmaceutical companies.

SOURCE: Olofsson T et al. Arthritis Care Res. 2020 May 20. doi: 10.1002/acr.24264.

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