Cochrane: Rituximab Is the Most Effective Biologic for RA

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.