Comparison trial shows two types of disease-modified drugs are equivalent
Rheumatoid arthritis is a complicated autoimmune disease to manage, especially in the more advanced stages. It is important that we stay abreast of the latest research, since RA is becoming more common (Arthritis Rheum. 2010 June;62(6):1576-1582). Recently, the prestigious European League Against Rheumatism (EULAR) Congress 2013 had its annual conference, so I thought it appropriate to discuss some of the findings. Most of the data is in abstract form and considered preliminary until the papers are fully published.
RA can be one of the most disabling diseases, with symptoms such as morning stiffness, diffuse joint pain and swelling that can affect multiple joints, with the proximal joints in the hands, wrists and feet most commonly affected bilaterally (Lancet. 2001;358(9285):903-911). It is not uncommon for RA patients also to be depressed, which can take its toll on productivity.
Medications used to treat RA involve disease-modifying antirheumatic drugs. One of the most common drugs used is methotrexate, which is frequently combined with tumor necrosis factors alpha inhibitors, such as Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab) and other DMARDs. We will discuss the benefits and drawbacks of TNF inhibitors, which have anti-inflammatory effects, but also suppress the immune system.
The goal of these drugs is to reduce synovitis, or inflammation in the joints, helping to lessen joint damage. They can be quite effective. Unfortunately, compliance can be an issue. Nonsteroidal anti-inflammatory drugs (NSAIDs) are also used for treatment, however, they should not be combined with methotrexate or at least caution should be advised when doing so.
Lifestyle modifications may also play a role in ameliorating RA, including helping with fall risk.
Even though there are a number of drug therapy options, compliance is an issue. In a recent study, approximately 33 percent of patients stopped or switched their RA medication within the first year, and by year two, the number increased to approximately half of patients (EULAR, Abstract OP0064). Patients on TNF inhibitors discontinued slightly less.
The main reason for discontinuation was a perceived lack of drug effectiveness, followed by side effects and therapy preferences. For those on TNF inhibitors, adverse reactions or safety were the main concerns. The greater the symptoms and progression of the disease, and the higher the psychological toll of the disease, such as depression and anxiety, the higher the probability that medication would be discontinued.
There were over 6,000 RA patients involved in this study, with disease duration averaging 11 years. The researchers used the Consortium of Rheumatology Researchers of North America registry to make this assessment.
Why might side effects be a concern for TNF inhibitors? In 2011, the FDA found there were 100 cases of Listeria and Legionella pneumonia infections associated with these drugs. Therefore, a warning was placed on all TNF inhibitors. The median duration that patients were on the drugs when they experienced infections was about 10 months. However, most patients were also on methotrexate and steroids at the time of infection.
While there were infections that took place during these drugs’ clinical trials, the absolute number was small. There was a large, though retrospective, study suggesting that the risk of serious infections requiring hospitalization is not greater than with other RA medications (JAMA. 2011;306:2331-2339).
Head-to-head trial of DMARDs or biologics
There was a recent head-to-head, blinded, randomized controlled trial, called the AMPLE trial, comparing two different types of DMARDs, Humira (adalimumab), a TNF inhibitor, and Orencia (abatacept), a non-TNF inhibitor (EULAR: Abstract OP0044). Both medications showed equivalent results in RA and are popular therapies for patients who have moderate to severe disease. Radiographic tests showed no joint damage progression in 85 percent of patients. However, there were fewer side effects with Orencia. Why is this important? Because if a patient can’t tolerate one drug, or if it does not work for them, then they can be confident that there are other, equally effective, options. This trial was two years in duration and involved 643 patients.
In one study, results showed that patients with early RA were more likely to apply for disability and subsequent early retirement due to depression than from symptoms of the disease, the level of work stress, other disease in combination with RA or the perceived effectiveness of drug therapy (EULAR: Abstract OP0092). Within the first year of being diagnosed with RA, depression outweighed other factors as a reason for disability by more than threefold.
The authors suggest that a questionnaire could help identify depressed patients so they could be treated appropriately, potentially preventing disability and early retirement. There were 563 patients involved in this study.
In a recent study involving 535 patients, results showed that RA patients have a greater probability of repeat falls (Arthritis Care Res. Online 2013 Feb. 22). This may not be surprising, considering the symptoms of joint stiffness, pain and swelling. The greatest predictor of future falls was a fall history. Therefore, patients with RA need to be asked about their tendency to fall. After the first fall, patients were three times as likely to fall again. Though history of fall was most valuable, symptoms of the disease, such as swollen joints and pain were also important. Interestingly, medications for treating depression contribute to fall risk. As we mentioned, RA patients have a higher tendency to be depressed. So what can be done to reduce fall risk? Lifestyle modifications with tai chi may be one option.
Lifestyle modifications include tai chi, diet, fish oil and aerobic exercise. I wrote about fish oil and aerobic exercise in my April 19, 2012, article entitled, “Rheumatoid arthritis effective management options.”
There was an extensive systematic review of the literature, which demonstrated that tai chi may have a role in reducing the risk of falls in RA by strengthening muscles and increasing flexibility (Br J Sports Med. 2012 Aug.;46(10):713-718). Unfortunately, tai chi did not have any effect on RA patients’ symptoms.
Since rheumatoid arthritis can be such a debilitating disease, both physically and mentally, it requires a significant partnership by the patient and doctor to treat it with medication and lifestyle modifications.
Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and consult your personal physician.