Enbrel vs. Remicade vs. Humira: Which Anti-TNF Drug Do RA Patients Stick With Longer?

Patient Expert

When living with RA, or any other chronic disease, finding an effective treatment is one of the most important goals in battling the destructive effects of the disease.   Fortunately, many rheumatologists begin patients on a disease-modifying anti-rheumatic drug (DMARD) soon after diagnosis.   Examples of treatment choices include triple therapy (methotrexate, hydroxychloroquine, and sulfasalazine), methotrexate alone, biologic agents, other traditional DMARDs, or a combination of any of the above.

In RA, something happens within the immune system that causes things to go awry.   Cells in the body which normally protect us from infection begin to attack normal cells.   The biologic agents used to treat RA are identified by the specific types of cells they target in the immune system.   Enbrel, Humira, Remicade, Cimzia, and Simponi are Tumor Necrosis Factor (TNF) inhibitors. Kineret and Actemra block Interleukins IL-1 and IL-6, respectively.   Orencia reduces T-cell activity and Rituxan depletes CD20+ B-cells. The newest biologic on the market, Xeljanz, inhibits Janus Kinases (JAK).

With each of these medications, it may take some time for them to achieve full effectiveness, anywhere from weeks to months.   Patients need to continue to use them as directed to gain the most benefit.   However, patients may not be able to tolerate a specific drug.   Or, a patient may not achieve a satisfactory response to the drug(s) and choose to try another one.

Determining which therapeutic approach will be most effective for an individual patient is one of the challenges of treating RA.   If one DMARD doesn't work well enough, it is common to move on to another one.   But how do we know which drug to start with and which one to try next?

In a recent study, researchers at the Hospital Clínico Universitario de Valladolid, Spain, took a closer look at the records of RA patients who were treated with select anti-TNF therapies between January 2011 and January 2012.   Researchers gathered demographic information and therapy assessments from medical and pharmaceutical records.   Staying on a treatment (also called drug survival or persistence of therapy) was presumed to be an overall marker of treatment success.

The primary objective of the study was to assess how long patients stayed on a particular anti-TNF drug and to identify potential predictors of drug discontinuation.   The overall goal of the study was to confirm whether or not current clinical practice is appropriate in terms of the choice of anti-TNF therapy for treating RA patients at this clinic.

Information analyzed in the study showed that predictors of drug survival in anti-TNF therapy for RA were: gender; being rheumatoid factor negative; being 60 years of age or older; and not having had previous treatment with anti-TNFs.   The risk of a change of treatment was lower for Humira and Enbrel than for Remicade.

During the 1-year study period, a group of 91 patients who had been given a total of 126 treatments were included in the study.   Women accounted for 72.5% of patients with average ages at the beginning of the study period of 54.6 and 58.8 years for men and women, respectively.   In addition to anti-TNF therapy, almost half of the patients were also using methotrexate.   64 patients (70%) continued with their initial biologic treatment, without needing to change to a different one. The remaining patients had to change treatment for various reasons.

The 126 treatments included infliximab (Remicade; n=53), etanercept (Enbrel; n=51), or adalimumab (Humira; n=22).   Certolizumab (Cimzia) and golimumab (Simponi) are not considered as they were not approved for use at the clinic at the time of the study.   Remicade was used most often as a first-line treatment, but researchers noted that it was the drug used for the shortest period of time before patients changed treatment.

The average time until a change of treatment for Remicade was 1,853 days with the drug survival rate dropping to approximately 20% after 2,200 days (6 years).   The average time until a change of treatment for Enbrel and Humira were 2,561 days and 2,769 days, respectively.   During the same time period that Remicade's drug survival rate fell to 20%, survival rates for Enbrel and Humira were 75% and 80%.

In patients who had not used another anti-TNF therapy previously, the average time until a change of treatment for Enbrel was greater than that of Remicade, 2,735 days versus 1,890 days.   Among patients who had previously been prescribed another anti-TNF drug, the average time until a change of treatment for Enbrel (1,987 days) was also greater when compared to Humira (1,327 days).   The probability of changing from Enbrel to another anti-TNF therapy was very low.

Women had the longest average time until a change in treatment with Humira (3,191 days), followed by Enbrel (2,659 days) and Remicade (1,743 days).   In men, the longest average time until treatment change was for Enbrel (2,224 days), followed by Remicade (1,545 days) and Humira (958 days).

When splitting the study population into two groups according to age - patients under the age of 60 years and those aged 60 years and older - statistical differences were noted.   On average, younger patients stayed with Enbrel the longest (2,421 days), followed by Humira (1,396 days) and Remicade (1,213 days).   In older patients, the average time until treatment change with Remicade was 2,559 days.   Older patients treated with Enbrel or Humira did not change to another anti-TNF therapy.

Authors conclude that choosing Remicade indiscriminately as a firstline anti-TNF therapy is not an appropriate practice, because starting a course of treatment with a drug that will probably become less effective over time will ultimately increase the overall cost of therapy.   Anti-TNF therapies should be chosen on the basis of patient characteristics, in order to ensure that treatment is successful.   As this study showed Enbrel to be superior to other anti-TNF agents across most of the subgroups, it would be good to conduct more research to discover why.

Martínez-Santana V, González-Sarmiento E, Calleja-Hernández MA, Sánchez-Sánchez T. Comparison of drug survival rates for tumor necrosis factor antagonists in rheumatoid arthritis.   Patient Prefer Adherence. 2013; 7: 719-727. Published online 2013 July 29. doi:   10.2147/PPA.S47453

Accessed at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764953/