Drug updates from April 2006

Taken from NRAS magazine, Spring 2006

New data shows HUMIRA® (adalimumab) provides real benefits to patients

A wealth of data will be presented at the British Society for Rheumatology meeting in May 2006 that reaffirms that HUMIRA® (adalimumab) provides effective results in managing rheumatological conditions including rheumatoid arthritis (RA) and psoriatic arthritis for which HUMIRA is licensed.

About Humira

• HUMIRA is prescribed as a fortnightly injection that can be self-administered from a pre-prepared syringe thus offering a convenient treatment option.
• Of the anti-TNFs available, HUMIRA is the only fully-human monoclonal antibody.
• Over 110,000 people worldwide have been prescribed HUMIRA to-date
• HUMIRA has been the subject of the largest clinical trial of any anti-TNF therapy involving over 6,000 patients. The ReAct trial looked at how patients respond to HUMIRA when it is taken in a real-life setting i.e. the way doctors would typically prescribe HUMIRA in their everyday practice.

The data to be present at BSR, along with other HUMIRA trial data already released show some important results including:

• In patients with early rheumatoid arthritis, HUMIRA in combination with methotrexate was superior to methotrexate alone in providing significant improvements in physical function and fatigue. (Results from the PREMIER trial.)
• In patients with early, aggressive RA, of those treated with HUMIRA combined with methotrexate who responded to treatmet, around 77% showed no joint damage, a much better outcome than for those treated with methotrexate alone.
  This benefit continued to increase during the 2 years of therapy followed up in the trial. (Results from the PREMIER trial.)
• In treating psoriatic arthritis, HUMIRA resulted in a 90% improvement in skin disease in 42% of patients. At the same
  time, as seen in RA, significant improvements in joint activity were demonstrated. (Results from the ADEPT trial.)

The first results from the PREMIER trial were originally presented last year at the EULAR conference, at which Professor Paul Emery, arc Professor of Rheumatology, Leeds University commented "The PREMIER data are very encouraging with over half the participants in the trial showing no disease progression after two years of treatment with adalimumab and methotrexate. These people have been able to retain considerable freedom and have avoided the pain and disability that would have been likely without treatment and clearly, these data point to the need to inhibit disease progression within the first six months of treatment".

U.S. Food And Drug Administration Approves Orencia® (abatacept) and Rituxan (rituximab) For The Treatment Of Rheumatoid Arthritis

In December the U.S. Food and Drug Administration (FDA) approved Orencia® (abatacept), the first selective modulator of a co-stimulatory signal required for full T-cell activation, for the treatment of rheumatoid arthritis (RA). (Basically, this means that this drug – exactly like the anti-TNF drugs – works by targeting a particular part of the immune system which is implicated in RA, i.e. T-cells, and by blocking the action of the T-Cells, reduces signs and symptoms of RA as well as slowing the progression of the disease).

In the States, Orencia is indicated for reducing the signs and symptoms of RA, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or anti-TNF treatment.

Orencia was studied in patients with an inadequate response to DMARDs. Specifically, it is the first approved agent to demonstrate efficacy and safety in patients with an inadequate response to anti-TNF treatments, as well as those with an inadequate response to MTX.

The efficacy and safety profiles of Orencia have been studied through a clinical trial program that included more than 2,600 patients.

In February FDA approval was given to market Rituxan, which in the UK is known as MabThera (rituximab), as a treatment for moderately-to-severely active rheumatoid arthritis.

MabThera is already widely used in its current indication of non-Hodgkin’s lymphoma and works by a different mechanism of action to all the available drugs for rheumatoid arthritis. (We provided a detailed description of MabThera in our last newsletter).

In America, MabThera has been approved for use alongside standard rheumatoid arthritis treatment methotrexate in patients who have not responded to anti-TNF therapy. MabThera requires only two injections a year, while most of the existing products need injections at least monthly. This low dosing frequency could also give the drug a pricing advantage.

Roche filed a regulatory submission for MabThera in rheumatoid arthritis to the European Medicines Agency (EMEA) in September 2005.

Methotrexate treatment for Rheumatoid Arthritis effective the second time

In February Theresa Kapral and colleagues from the Medical University of Vienna, published a study showing a second course of methotrexate, the most commonly used drug to treat rheumatoid arthritis, was effective in nearly half of the seventy-nine studied patients for whom a previous treatment with the drug was ineffective. The results which were published in Arthritis Research & Therapy also showed that a second treatment with methotrexate was particularly effective in patients who were given low dose methotrexate in their first treatment.

The second treatment was more than twice as likely to be successful if the methotrexate dose in the first treatment had been lower or equal to 10mg per week than if it had been greater than 17.5mg per week.

The results of this study indicate that renewed institution of methotrexate might be one option that could be considered for the treatment of patients.

Golimumab shows early promise

At the meeting of the American College of Rheumatology (ACR) at the end of 2005, a study of golimumab (CNTO 148) showed promising results.

Golimumab is a human monoclonal antibody being developed for the treatment of rheumatoid arthritis and other immune-mediated inflammatory diseases.

This study, early in the development of golimumab, showed that patients with rheumatoid arthritis who do not respond to methotrexate may have another option in golimumab. Subcutaneous injections of the biologic given at two or four week intervals effectively reduced signs and symptoms of RA and was generally well tolerated with no unexpected safety concerns.

"The results of this trial demonstrate the potential of CNTO 148 as another therapy for the treatment of rheumatoid arthritis," said Dr Jonathan Kay, Associate Clinical Professor of Medicine at Harvard Medical School, Director of Clinical Trials in the Rheumatology Unit at Massachusetts General Hospital, and lead author on the study.

Belimumab, early promise?

The results of an early (called phase 2) trial of belimumab in rheumatoid arthritis were presented for the first time at the Annual Scientific Meeting of the ACR.

The study was conducted in 283 patients with active moderate-to-severe disease who had failed prior treatment. Belimumab was administered intravenously for 24 weeks.

The results showed that the drug was safe and well tolerated and that it had a statistically significant beneficial effect on reducing RA activity, warranting further studies for rheumatoid arthritis. But several RA experts have commented that the efficacy observed was rather modest, and in view of the fact that there are very effective drugs for RA already available, some are wondering how clinically useful this approach, known as anti-BLyS, will turn out to be. Belimumab may find a place in the therapeutic armamentarium for management of rheumatoid arthritis and related conditions if further studies demonstrate a consistent and significant pattern of efficacy.

Cannabis-based medicine (Sativex) relieves the pain of rheumatoid arthritis and suppresses the disease

The first study to use a cannabis-based medicine (CBM) for treating rheumatoid arthritis has found that it has a significant effect on easing pain and on suppressing the disease.

Writing in the medical journal Rheumatology, which is the official monthly journal of the British Society for Rheumatology (BSR), researchers say that although the differences were small and variable in the group of 56 patients they studied, the results are statistically significant and a larger trial is needed to investigate in more detail the effects of cannabis-based medicine (CBM) on rheumatoid arthritis.