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Meta-analysis: Auranofin is the least effective and injectable gold is the most toxic of second-line drugs for rheumatoid arthritis

ACP J Club. 1991 Mar-Apr;114:43. doi:10.7326/ACPJC-1991-114-2-043

Source Citation

Felson DT, Anderson JJ, Meenan RF. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum. 1990 Oct;33:1449-61.



To evaluate the efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs in treating rheumatoid arthritis.

Data sources

Studies published from January 1966 through August 1989 in which second-line agents were used to treat rheumatoid arthritis were identified using MEDLINE. Bibliographies from identified articles were also scanned.

Study selection

Articles were censored for potentially biasing information before the review. Criteria for inclusion in the meta-analyses were as follows: patients were ≥ 18 years old; at least 90% of the patients had rheumatoid arthritis; assignment to treatment was by a random or quasi-random method; the trial was either placebo-controlled or was a comparative trial; and the follow-up was ≥ 2 months. For the efficacy analysis, studies had to provide evidence on improvement in tender joint count, grip strength, or erythrocyte sedimentation rate. In addition, for the toxicity analysis, the number of patients who dropped out because of adverse effects had to be reported.

Data extraction

The quality of each trial was independently rated for information about eligibility criteria, random allocation, blinding, treatment complications, patients lost to follow-up, statistical analysis, the names of particular techniques, and whether a power analysis was done.

Data synthesis

Of 168 studies reviewed, 66 met the inclusion criteria. For each of the 3 outcome measures, AUR was weaker than other second-line drugs. When all 3 outcome measures were combined into a composite score, AUR was weaker than MTX (P = 0.006), injectable gold (P < 0.001), DP (P < 0.001), and SSZ (P = 0.009), and slightly weaker than antimalarial agents (P = 0.11). Little difference in efficacy was found between MTX, injectable gold, DP, and SSZ. For the toxicity analysis, 71 studies met the inclusion criteria. Injectable gold had the highest toxicity rates (P < 0.05) and the highest total drop-out rates (P < 0.01). Antimalarial drugs and AUR had relatively low toxicity rates.


Auranofin is less effective than most other second-line drugs for rheumatoid arthritis, and injectable gold has the highest toxicity.

Source of funding: National Institutes of Health.

Address for article reprint: Dr. D.T. Felson, Arthritis Center, A-203, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA.


Studies of the relative efficacy and toxicity of the commonly used second-line antirheumatic drugs have been plagued by their low statistical power because of relatively small numbers of patients. This large analysis of studies has confirmed important clinical impressions and yielded new insights regarding these agents.

When auranofin was initially introduced, it was hoped that this oral form of gold would have fewer side effects, but retain comparable clinical efficacy compared with injectable gold salts. This study has confirmed the low rate of toxicity of auranofin, but, unfortunately, has also confirmed the impression among rheumatologists that auranofin is less effective than injectable gold.

It is of interest that injectable gold was shown to be more toxic than other second-line drugs. Many U.S. rheumatologists believe that injectable gold is less toxic than D-penicillamine and has equal toxicity rates to other second-line drugs. Largely because of this impression, U.S. rheumatologists tend to use injectable gold earlier and more often than other second-line drugs. The results of this meta-analysis suggest that gold is more toxic and no more effective than other second-line drugs. These other drugs, including methotrexate and sulfasalazine, may assume a greater role in the treatment of rheumatoid arthritis. Of the drugs reviewed, antimalarial drugs, D-penicillamine, methotrexate, and sulfasalazine appear to have the most favorable balance of benefit and toxicity.

Robert A. Hawkins, MD
Wright State UniversityDayton, Ohio, USA