Noninflammatory Pain Persists in RA Despite Treatment Save
Almost one-third of patients with new-onset rheumatoid arthritis (RA) reported persistent unacceptable pain after 21 months of combination therapy, according to a study by Swedish researchers.
A total of 29% of patients continued to have unacceptable pain, defined as a score above 40 mm on a 100 mm visual analog scale, after 21 months of treatment with either methotrexate plus infliximab (Remicade) or methotrexate plus sulfasalazine and hydroxychloroquine, said Tor Olofsson, MD, PhD, of Lund University, and colleagues.
In addition, as they reported in the study online in Arthritis Care & Research, refractory pain, defined as unacceptable pain despite inflammation control -- C-reactive protein (CRP) level below 10 mg/L -- represented four-fifths of the pain load after 21 months of combination treatment.
Pain in RA has traditionally been considered an inflammatory process centered on the synovium, but reports have suggested that persistent pain troubles many patients even if they otherwise responded to treatment and achieved low disease activity.
"Fibromyalgia is present in up to 25% of RA patients (compared to 2% in the general population), lending further support to a multifaceted pain spectrum in RA consisting of both inflammation-derived and inflammation-independent pain components," Olofsson and co-authors wrote.
Recent randomized trials have found that methotrexate plus either a tumor necrosis factor inhibitor or sulfasalazine/hydroxychloroquine (triple therapy) can successfully decrease conventional disease activity measures, but no data are available on how the two therapeutic approaches influence the different components of pain, the team noted.
The researchers therefore conducted a post-hoc analysis of data from their SWEFOT cohort, which enrolled patients from 15 Swedish centers from 2002 to 2005. Participants in that trial were given methotrexate for 3 months, and those who did not achieve low disease activity, defined as a Disease Activity Score in 28 joints (DAS28) of 3.2 or lower, were randomized to receive infliximab, 3 mg/kg every 8 weeks, or sulfasalazine, 1,000 mg twice daily plus hydroxychloroquine, 400 mg once daily. All patients continued on methotrexate.
Of the 487 patients who initiated methotrexate treatment, 258 had not reached a state of low disease activity after 3 months and were randomized to one of the two regimens. Participants were then followed for an additional 21 months.
At the time of randomization, patients in both groups had high disease activity, with a DAS28 of almost 6, and also had substantial pain, with an average score of almost 60 mm on the 100 mm visual analog scale.
The patients in the two groups were similar, with an average age of 53, and the majority were women. Symptom duration was slightly over 6 months, and the average number of swollen joints was 11.
Among patients who were randomized, 81% had reported an unacceptable level of pain at the time they enrolled in the study. This number decreased to 50% by the time they underwent randomization, when the mean pain score was 43.
At the time of study enrollment, 53% of the pain was considered inflammatory, in that the pain score was above 40 and CRP was 10 mg/L or higher; this declined to 19% by the time of randomization and to 5% at 21 months (P<0.001). Refractory pain, in contrast, was consistent throughout follow-up at 25-30%, and represented 82% of all unacceptable pain at 2 years, the researchers calculated.
The relative risk of still having unacceptable pain after 21 months was lower in the infliximab group than in the triple-therapy group (RR 0.68, 95% CI 0.51-0.90, P=0.008). For unacceptable inflammatory pain, the infliximab group again had lower risks at month 21 (RR 0.48, 95% CI 0.24-0.93, P=0.031). In addition, the area under the curve for cumulative pain was lower in the infliximab group.
However, for refractory pain (unacceptable pain despite inflammation control suggesting a noninflammatory cause) at 21 months, the infliximab group had only a nonsignificant lower rate (23% vs 28%, P=0.27).
"Hence, whereas nociceptive pain in RA patients -- elicited by a normal somatosensory nervous system as a response to inflammation -- generally responds well to immunosuppressive agents, our results strengthen the evidence that current therapy regimens are insufficient in preventing the occurrence of noninflammatory pain components, often arising from central sensitization (increased responsiveness to stimuli in the central nervous system)," the authors observed.
They concluded that RA treatment strategies need to more fully address the inflammation-independent aspects of pain.
A limitation of the study, the team said, was the open label design.
Disclosures
The study, a post-hoc analysis of the SWEFOT trial, was supported by Lund University, the Koshka Foundation, the Swedish Research Council, and the Stockholm County Council.
Olofsson reported having no competing interests; co-authors reported financial relationships with AbbVie, Celgene, Eli Lilly, Novartis, UCB, AstraZeneca, Biogen, Biotest, Bristol Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Pfizer, and Servier.
Primary Source
Arthritis Care & Research
If you are a health practitioner, you may Login/Register to comment.
Due to the nature of these comment forums, only health practitioners are allowed to comment at this time.