I Have Rheumatoid Arthritis And Have Heard About Golimumab… What Is It?

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease for which there is no current cure. However, the advent of biologic therapy has made it possible to induce remission in the majority of patients.

However, in order to effect remission, research suggests that a critical therapeutic window may exist within the first two years of disease onset when the rate of x-ray progression of the disease- which correlates directly with potential disability- can be slowed. X-ray changes occur within two years of disease onset in 50-70 percent of RA patients.

Many experts have suggested control of disease progression should start early to limit joint damage in RA. RA is associated with substantial disability and economic losses.

Most studies have shown that a combination of methotrexate and TNF-inhibitors work effectively to slow x-ray progression and improve daily functioning. TNF-inhibors include drugs such as etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). A second generation of biologics has become available for use in patients who fail first line treatment. These include drugs such as abatacept (Orencia) and rituximab (Rituxan).

Newer biologic drugs are currently under study. One such drug is golimumab. Golimumab (Centocor, Schering-Plough) is a fully-human TNF-inhibitor monoclonal antibody that targets and neutralizes both the soluble and the membrane-bound form of TNF-alpha. Golimumab is being investigated for administration by subcutaneous (SC) injection and intravenous (IV) infusion.

In RA clinical trials in the U.S., patient responses to treatment are measured using the American College of Rheumatology (ACR) response of 20% (ACR 20), 40% (ACR 50), and 70% (ACR 70). In other words, if a patient has a 20 percent response to treatment, they have an ACR 20 response. If they have a 50 percent response to treatment they have reached ACR 50… and so on. The greater the number of patients reaching a higher ACR level the more effective the treatment.

The greater the number of patients responding at a given ACR level, the better the drug.

For instance, a drug that gives an ACR 70 response of 40 percent is much better than a drug that gives an ACR 70 response of 20 percent.

According to new findings presented from a double-blind, placebo-controlled, dose-ranging Phase 2 study, nearly 75 percent of patients with moderately to severely active rheumatoid arthritis (RA) receiving golimumab (CNTO 148) and methotrexate experienced at least 20 percent improvement in arthritis symptoms (ACR 20) at one year.

Investigators also reported that more than one-third of patients treated with golimumab and methotrexate achieved remission at one year.

In this preliminary study of the effects of golimumab in RA, 172 adults with active RA for at least three months' duration despite methotrexate therapy were randomized to one of five treatment groups: placebo every two weeks or golimumab 50 or 100 mg every two weeks or every four weeks.

All patients received stable doses of methotrexate of at least 10 mg/week. At week 16, 62 percent, 31 percent and 12 percent of all patients receiving golimumab (combined golimumab treatment groups) plus methotrexate experienced ACR 20, ACR 50 and ACR 70 improvements, respectively, compared with 37 percent, 6 percent and zero percent of patients receiving placebo plus methotrexate, respectively.

At week 52 of the study, ACR 20, ACR 50 and ACR 70 scores improved to 74 percent, 45 percent and 22 percent respectively, among patients receiving golimumab plus methotrexate (combined golimumab treatment groups). Moreover, patients receiving 50 mg every two weeks and 100 mg every two weeks maintained efficacy through week 52, even after converting to every four weeks administration at week 20.

Patients receiving golimumab plus methotrexate also achieved remission, as assessed by the abbreviated disease activity scale (DAS 28), which measures tender and swollen joints, inflammation and overall disease activity including measurement of erythrocyte sedimentation rate (ESR). A DAS 28 of less than 2.6 indicates remission.

After 16 weeks of treatment, 27 percent of patients in the golimumab (combined golimumab treatment groups) plus methotrexate group achieved remission as assessed by DAS28 (DAS < 2.6) compared with six percent of patients receiving placebo plus methotrexate. Similar remission rates were reported at week 52, with 34 percent of patients receiving golimumab plus methotrexate achieving remission at that time point. All of these results were statistically significant.

Golimumab was generally well tolerated in the study through week 52. Serious adverse events (AEs) reported were eight percent for the combined golimumab groups compared with six percent for the placebo group. No deaths, cases of tuberculosis or other opportunistic infections were reported through 52 weeks, and serious infections were uncommon. The most common clinically relevant serious AEs through week 52 were pneumonia (three patients), lung cancer (one patient), cardiac tamponade (one patient), and cardiac failure (one patient). One patient died from coronary artery disease approximately four months after completing 52 weeks of the study.

While these adverse events appear serious (and they are), they are not worse than what is usually seen in clinical trials involving RA. RA is not a benign disease and patients will develop medical problems that are not necessarily related to the medication being studied. However, all adverse events have to be reported.

The results from this early (phase 2) study shows promise. Through the development of new drugs and through the further investigation of mechanisms of disease, a cure for RA will be found, hopefully, in the now too distant future.