Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use

Abstract

BackgroundThe effects of fish oil (FO) in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA. This study examined the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).MethodsPatients with RA <12 months’ duration and who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or low dose (for masking). These groups, designated FO and control, were given 5.5 or 0.4 g/day, respectively, of the omega-3 fats, eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.ResultsIn the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.ConclusionsFO 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.

Endogenous conversion of n-6 to n-3 polyunsaturated fatty acids attenuates K/BxN serum-transfer arthritis in fat-1 mice

“…Eskimos consuming large amounts of fish oil report a lower incidence of RA [46]. In a recent double-blind controlled study, RA patients treated with 5.5 g of n-3 PUFAs/day showed reduced treatment failure and a higher rate of achievement of disease remission [47]. The question of whether the ratio of n-6/n-3 PUFAs or total amount of dietary n-3 PUFA intake is of great concern.…”

Plasma Levels of Eicosapentaenoic Acid Are Associated with Anti-TNF Responsiveness in Rheumatoid Arthritis and Inhibit the Etanercept-driven Rise in Th17 Cell Differentiationin Vitro

“…Beneficial effects continue to be seen when fish oil is added to triple DMARD therapy with a treat-to-target approach in early RA. 26 In this study we sought to determine whether plasma levels of n-3 fatty acids correlated with response to anti-TNF in RA, and propose and test a mechanistic hypothesis for the heightened responsiveness we observed in association with higher EPA levels in the absence of high dose fish oil supplementation.…”

Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose

“…Although NSAIDs transiently reduce knee OA pain, due to the adverse effects, American College of Rheumatology (ACR) guidelines recommend intermittent use only 2. A systematic review of fish oil use in rheumatoid arthritis (RA) reported decreased NSAID use with fish oil,3 and a randomised controlled trial (RCT) of high-dose fish oil in recent-onset RA demonstrated a higher remission rate 4. Synovial inflammation is associated with severity of pain in knee OA5–7 and has been variably associated with cartilage loss 7 8.…”