New hope for patients with debilitating arthritis

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Twenty years ago, steroid injections, bed rest, aspirin, and lengthy hospital stays were some of the treatments that millions of children and adults living with rheumatoid arthritis in Canada used to manage their unbearable pain. Today, most people with rheumatoid arthritis can effectively use anti-rheumatic drugs and don’t need to be admitted to hospital. Yet, these drugs are unable to help 25 per cent of people with arthritis. To help these people, there are promising new drugs called biologics. Also known as biological response modifiers, these new medications are genetically-engineered protein molecules. They are designed to target molecules such as TNF-alpha cytokines. Cytokines are a special type of protein secreted by the body’s immune system and linked to the painful joint inflammation that characterizes several types of arthritis. Once injected into patients, biologics begin soaking up excess cytokines, thus reducing symptoms of arthritis.

“Biologics were first used with rheumatoid arthritis patients who didn’t respond to standard medications,” says Dr. Arthur Bookman, rheumatologist at Toronto Western Hospital (TWH). “Now, we are also prescribing biologics for patients with other types of arthritis associated with severe inflammation, such as psoriatic arthritis and ankylosing spondylitis.” Psoriatic arthritis (PsA) is a condition marked by joint inflammation and a scaly rash on the skin. Ankylosing spondylitis (AS) is a type of arthritis that affects the spine and spinal joints. Left untreated, AS can cause extreme stiffness and immobility.

Biologics have proven to be effective for people with PsA. Through the hospital’s Psoriatic Arthritis Clinic, Dr. Dafna Gladman, TWH rheumatologist and head of the hospital’s Psoriatic Arthritis Program, has followed the prognosis of approximately 800 patients, which is the largest and most comprehensively studied group of PsA patients in the world. These studies have enabled Dr. Gladman and her colleagues to evaluate new treatments such as biologics and to assess the impact of these treatments on patients’ quality of life.

“Through our investigations, we’ve seen that the biologic infliximab can be effective in treating skin and joint symptoms for severe cases of PsA,” says Dr. Gladman. “Through our longitudinal prognosis studies, we’ve learned that we need to treat PsA more aggressively earlier in the course of the disease. We’re also discovering, through the ongoing clinical research, that if biologics are given to patients early enough, the disease progression of PsA and AS can be stopped.”

Dr. Gladman is also conducting investigations to identify the genes responsible for the severity of PsA. “If we can find the gene, then we would be able to identify people who will go on to develop more severe forms of PsA,” she explains, “and we would be alerted to which patients should be treated more aggressively earlier on in the course of the disease.” Early diagnosis and treatment are crucial to preventing long-term deformities and mobility issues that arise from arthritis.

Presently, Dr. Gladman is involved in the first international clinical trial for a new biologic called adalimumab, to determine its effectiveness for treating PsA. Dr. Bookman is involved with a multi-centre Canadian clinical trial for using adalimumab to treat rheumatoid arthritis, for which it is already approved in the U.S.

“We want to bring this drug to Canada because it offers several advantages,” notes Dr. Bookman. One significant advantage is the fact that this particular agent is a purely human protein, which means reduced allergic reactions for patients. Adalimumab can also be given to patients every two weeks, whereas other anti-TNF agents are injected twice weekly or need to be given intravenously.

Dr.Robert Inman, TWH rheumatologist, research scientist and Director of UHN’s Arthritis Centre of Excellence, is playing a leadership role in a Canada-led study on the effectiveness in adalimumab in treating AS. “We are particularly excited about this study since it has been developed by a group of Canadian rheumatologists and it has set the stage for a large study to follow in Europe and the U.S.,” said Dr. Inman.

As part of an international research study spanning five countries, Dr. Inman has recently published that one biologic called etanercept is particularly effective for patients with AS. “We found that after six months, etanercept results in reduced pain and improved mobility for people suffering from AS,” said Dr. Inman. Prior to the development of biologics, there were few effective therapies available for treating AS. “The era of biologic therapy has introduced new hope for patients who otherwise would be facing a lifetime of pain and disability,” comments Dr. Inman. He adds that studies are ongoing at TWH to identify the immune and genetic profile of AS patients who are most likely to benefit from these new forms of treatment.

According to the Arthritis Society of Canada, 70 per cent of patients treated with biologics experience some degree of symptom improvement within a relatively short period of time. Patients can notice improvement within two weeks of starting treatment with a biologic, compared to other types of anti-rheumatic drugs, which can take up to two months. In addition, since the body’s organs do not process biologics, patients have very little risk of experiencing internal organ toxicity. This is comforting news for patients, since many conventional medications are known to cause kidney or liver damage. Patients using biologics can experience side effects and these tend to be limited to headaches and a mild skin reaction at the site of injection. Infection can occur somewhat more frequently on these agents, and old tuberculosis can be reactivated unless precautions are followed to prevent this. It is important to note that while the anti-TNF agents are proven for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, not all patients may be eligible to use these medications.