Fish oil enhances triple therapy increasing remission rates
The effects of fish oil (FO) in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA.
In this new study Dr. Susanna M. Proudman, MD, Professor, Rheumatology Unit, Royal Adelaide Hospital and colleagues examined the effects of high versus low dose fish oil in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).
Dr. Proudman and colleagues enrolled 140 patients with early RA (under 12 months) and were randomly assigned to receive fish oil at high dose level 5.5g daily or low dose level 0.4g/day or EPA plus DHA. The low dose group served as the control group due to the fact the low dosage has not been associated to clinical effects in past studies.
All patients received methotrexate (Trexall) 10mg weekly), sulphasalazine (Azulfidine 500mg daily) and hydroxychloroquine (Plaquenil 200mg twice daily), and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account.
Dosages could be increased in a structured fashion if the swollen joint count remained at two or higher, if the erythrocyte sedimentation rate or C-reactive protein level remained elevated, or if pain, fatigue, or early morning stiffness persisted.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) and oral corticosteroids was discouraged.
Treatment failure was defined as the need to add leflunomide (Arava) to the triple regimen.
DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly.
At the one year mark, 10.5% of patients taking the fish oil and 32.1% of the control group had begun taking leflunomide.
The failure rate remained significantly lower for the fish oil group after adjustment for smoking, baseline anti-cyclic citrullinated peptide, and shared epitope (HR 0.24, 95% CI 0.10-0.54, P=0.0006). The remission rate was also significantly greater after adjusting for the factors.
No difference was noticed in the number of patients who required steroids during the trial period and mean methotrexate doses showed no difference between the two groups.
At the start of this study 38% of participants in the fish oil group and 34% in the control group were taking NSAIDS but after one year only one participant in the control were still taking NSAIDS.
There were no differences between the groups for adverse events. Even though serious adverse events had been higher in the fish oil group there was no pattern to suggest a linkage with fish oil.
In their conclusion the team writes “FO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.”
The researchers explained that fish would provide benefits in RA due to the ability of omega-3 fatty acids to inhibit the release of inflammatory mediators and peptides, including prostaglandin E2 and leukotriene B4, as well as tumor necrosis factor alpha, all of which are targets of current treatments.
They also noted that only patient had progressed to biological treatment by one year which suggests a probable cost savings with fish oil and conventional triple therapy, in that it may "at least delay progression to biologic therapy."