Therapeutics
In patients with early rheumatoid arthritis, fish oil reduced failure of treatment with DMARDs
Proudman SM, James MJ, Spargo LD, et al. Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis. 2013: Sep 30. [Epub ahead of print]
Clinical impact ratings: F ★★★★★✩✩ R ★★★★★★✩ Question In patients with early rheumatoid arthritis (RA), what is the effect of adding fish oil to treatment with disease-modifying antirheumatic drugs (DMARDs)?
Score [DAS] 28 ≤ 3.2), disease activity (DAS28), and activities of daily living (modified Health Assessment Questionnaire). Patient follow-up: 87% (intention-to-treat analysis).
Main results
Methods Design: Randomized controlled trial. Australian New Zealand Clinical Trials Registry ACTRN12613000579796.
The main results are in the Table. Groups did not differ for disease activity or activities of daily living.
Conclusion
Allocation: Concealed.* Blinding: Blinded* (patients, {clinicians, data collectors, data analysts}†, and outcome assessors).
In patients with early rheumatoid arthritis, fish oil reduced failure of treatment with disease-modifying antirheumatic drugs.
Follow-up period: 1 year.
*See Glossary.
Setting: Early Arthritis Clinic, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
†Information provided by author.
Patients: 140 adults ≥ 18 years of age (mean age 56 y, 73% women) who had RA, with polyarthritis for < 12 months, ≥ 3 swollen joints, and erythrocyte sedimentation rate ≥ 28 mm/h or C-reactive protein ≥ 10 mg/dL, and who had not been treated with DMARDs. Exclusion criteria included antimalarial treatment for > 1 month; antinuclear antibody titer ≥ 1:320; hepatitis B or C or HIV infection; sensitivity to methotrexate, sulfasalazine, or hydroxychloroquine; or systemic disease likely to increase risk for toxicity to ≥ 1 of these drugs. Intervention: Patients were randomized in a 2:1 ratio to highdose fish oil (fish oil concentrate, 10 mL/d [BLT Incromega TG3525], which provides 5.5 g/d eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) (n = 87); or low-dose fish oil (2:1 sunola oil–capelin oil, 10 mL/d, which provides 0.4 g/d EPA plus DHA) (n = 53), added to algorithm-based DMARD treatment that was responsive to disease activity and toxicity. Outcomes: Primary outcome was failure of triple DMARD therapy (with progression to leflunamide). Secondary outcomes included serious adverse events, remission, European League Against Rheumatism (EULAR) good response (Disease Activity High- vs low-dose fish oil added to disease-modifying antirheumatic drugs in early rheumatoid arthritis‡ Outcomes
Event rates High Low
Failure of DMARDs§
10%
Serious adverse events
12%
32% 3.8%
At 1 y RRR/RRI (95% CI) RRR 67% (33 to 84) RRI 208% (−20 to 1127)
NNT 5 (3 to 13) NS
aHR (CI) ACR remission|| EULAR good response**
25%¶
17%¶
2.09 (1.02 to 4.30)
NR
NR
1.41 (0.89 to 2.21)
‡ACR = American College of Rheumatology; aHR = adjusted hazard ratio; DMARDs = disease-modifying antirheumatic drugs; EULAR = European League Against Rheumatism; NR = not reported; NS = not significant; other abbreviations defined in Glossary. RRR, RRI, and CI calculated from event rates in article. Hazard ratio adjusted for smoking history and anticyclic citrullinated and shared epitope.
Sources of funding: National Health Medical Research Council of Australia and Royal Adelaide Hospital Research Committee. For correspondence: Professor S.M. Proudman, Royal Adelaide Hospital, Adelaide, South Australia, Australia. E-mail [email protected]. ■
Commentary Early treatment with multiple drugs is the standard strategy for achieving complete suppression of disease activity and long-term remission in RA. The role of (generally expensive) biological agents in early treatment has yet to be fully explored. Moreover, there is ongoing interest in treatments that might also reduce dependency on potentially hazardous nonsteroidal antiinflammatory drugs. The antiinflammatory effect of fish oils has been established in previous treatment regimens, and the results of the carefully conducted trial by Proudman and colleagues suggest that fish oils may be effective in patients who are receiving intensive early treatment. The authors also point out that these supplements may reduce the increased risk for cardiovascular disease in RA patients. However, some points should be clarified before fish oils become part of standard practice. First, 1 year is a short period of observation in a potentially chronic disease. Second, RA is a heterogeneous disease, and patients in this trial were diagnosed according to criteria that have since been updated (1), with only 53% of treated patients positive for cyclic citrullinated peptide, the autoantibody most diagnostically specific for this disorder (2). This heterogeneity probably explains why not all patients diagnosed with early RA respond to the current array of antiinflammatory agents. Finally, some patients did not comply with their prescribed schedules, which suggests that not all patients would be able to tolerate long-term fish oil supplementation. Extended trials are needed. The study by Proudman and colleagues shows that investigators are willing to endorse lifestyle recommendations for managing RA once their efficacy has been scrutinized through rigorous scientific appraisal. Michael Denman, MD Northwick Park Hospital Harrow, England, UK
§aHR 0.24, CI 0.10 to 0.54. ||American College of Rheumatology criteria. ¶Information provided by author. **Disease Activity Score 28 ≤ 3.2.
18 February 2014 | ACP Journal Club | Volume 160 • Number 4
References 1. Berglin E, Dahlqvist SR. Scand J Rheumatol. 2013;42:362-8. 2. van Venrooij WJ, van Beers JJ, Pruijn GJ. Nat Rev Rheumatol. 2011; 7:391-8.
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/929769/ by a Tufts University User on 07/27/2017
JC11
In patients with early rheumatoid arthritis, fish oil reduced failure of treatment with DMARDs
Proudman SM, James MJ, Spargo LD, et al. Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis. 2013: Sep 30. [Epub ahead of print]
Clinical impact ratings: F ★★★★★✩✩ R ★★★★★★✩ Question In patients with early rheumatoid arthritis (RA), what is the effect of adding fish oil to treatment with disease-modifying antirheumatic drugs (DMARDs)?
Score [DAS] 28 ≤ 3.2), disease activity (DAS28), and activities of daily living (modified Health Assessment Questionnaire). Patient follow-up: 87% (intention-to-treat analysis).
Main results
Methods Design: Randomized controlled trial. Australian New Zealand Clinical Trials Registry ACTRN12613000579796.
The main results are in the Table. Groups did not differ for disease activity or activities of daily living.
Conclusion
Allocation: Concealed.* Blinding: Blinded* (patients, {clinicians, data collectors, data analysts}†, and outcome assessors).
In patients with early rheumatoid arthritis, fish oil reduced failure of treatment with disease-modifying antirheumatic drugs.
Follow-up period: 1 year.
*See Glossary.
Setting: Early Arthritis Clinic, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
†Information provided by author.
Patients: 140 adults ≥ 18 years of age (mean age 56 y, 73% women) who had RA, with polyarthritis for < 12 months, ≥ 3 swollen joints, and erythrocyte sedimentation rate ≥ 28 mm/h or C-reactive protein ≥ 10 mg/dL, and who had not been treated with DMARDs. Exclusion criteria included antimalarial treatment for > 1 month; antinuclear antibody titer ≥ 1:320; hepatitis B or C or HIV infection; sensitivity to methotrexate, sulfasalazine, or hydroxychloroquine; or systemic disease likely to increase risk for toxicity to ≥ 1 of these drugs. Intervention: Patients were randomized in a 2:1 ratio to highdose fish oil (fish oil concentrate, 10 mL/d [BLT Incromega TG3525], which provides 5.5 g/d eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) (n = 87); or low-dose fish oil (2:1 sunola oil–capelin oil, 10 mL/d, which provides 0.4 g/d EPA plus DHA) (n = 53), added to algorithm-based DMARD treatment that was responsive to disease activity and toxicity. Outcomes: Primary outcome was failure of triple DMARD therapy (with progression to leflunamide). Secondary outcomes included serious adverse events, remission, European League Against Rheumatism (EULAR) good response (Disease Activity High- vs low-dose fish oil added to disease-modifying antirheumatic drugs in early rheumatoid arthritis‡ Outcomes
Event rates High Low
Failure of DMARDs§
10%
Serious adverse events
12%
32% 3.8%
At 1 y RRR/RRI (95% CI) RRR 67% (33 to 84) RRI 208% (−20 to 1127)
NNT 5 (3 to 13) NS
aHR (CI) ACR remission|| EULAR good response**
25%¶
17%¶
2.09 (1.02 to 4.30)
NR
NR
1.41 (0.89 to 2.21)
‡ACR = American College of Rheumatology; aHR = adjusted hazard ratio; DMARDs = disease-modifying antirheumatic drugs; EULAR = European League Against Rheumatism; NR = not reported; NS = not significant; other abbreviations defined in Glossary. RRR, RRI, and CI calculated from event rates in article. Hazard ratio adjusted for smoking history and anticyclic citrullinated and shared epitope.
Sources of funding: National Health Medical Research Council of Australia and Royal Adelaide Hospital Research Committee. For correspondence: Professor S.M. Proudman, Royal Adelaide Hospital, Adelaide, South Australia, Australia. E-mail [email protected]. ■
Commentary Early treatment with multiple drugs is the standard strategy for achieving complete suppression of disease activity and long-term remission in RA. The role of (generally expensive) biological agents in early treatment has yet to be fully explored. Moreover, there is ongoing interest in treatments that might also reduce dependency on potentially hazardous nonsteroidal antiinflammatory drugs. The antiinflammatory effect of fish oils has been established in previous treatment regimens, and the results of the carefully conducted trial by Proudman and colleagues suggest that fish oils may be effective in patients who are receiving intensive early treatment. The authors also point out that these supplements may reduce the increased risk for cardiovascular disease in RA patients. However, some points should be clarified before fish oils become part of standard practice. First, 1 year is a short period of observation in a potentially chronic disease. Second, RA is a heterogeneous disease, and patients in this trial were diagnosed according to criteria that have since been updated (1), with only 53% of treated patients positive for cyclic citrullinated peptide, the autoantibody most diagnostically specific for this disorder (2). This heterogeneity probably explains why not all patients diagnosed with early RA respond to the current array of antiinflammatory agents. Finally, some patients did not comply with their prescribed schedules, which suggests that not all patients would be able to tolerate long-term fish oil supplementation. Extended trials are needed. The study by Proudman and colleagues shows that investigators are willing to endorse lifestyle recommendations for managing RA once their efficacy has been scrutinized through rigorous scientific appraisal. Michael Denman, MD Northwick Park Hospital Harrow, England, UK
§aHR 0.24, CI 0.10 to 0.54. ||American College of Rheumatology criteria. ¶Information provided by author. **Disease Activity Score 28 ≤ 3.2.
18 February 2014 | ACP Journal Club | Volume 160 • Number 4
References 1. Berglin E, Dahlqvist SR. Scand J Rheumatol. 2013;42:362-8. 2. van Venrooij WJ, van Beers JJ, Pruijn GJ. Nat Rev Rheumatol. 2011; 7:391-8.
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/929769/ by a Tufts University User on 07/27/2017
JC11
