RA needs Joint working between Consultant Rheumatologists and GPs
Due to all the new treatments, RA patients can experience remission or at least very low disease activity.
GPs see more patients for musculoskeletal problems than anything else. High up the list of these problems and one of the most debilitating is Rheumatoid Arthritis. The good news is that the disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate are effective at reducing joint destruction and improving quality of life. However, some patients do not tolerate methotrexate well and can develop drug toxicity.
So, the newer drugs known as biologics (such as adalimumab and etanercept) have significantly improved the control of RA. The types of drugs and of treatment options is summarised by RA expert, Consultant Rheumatologist, Dr Pamela Mangat - http://www.totalhealth.co.uk/clinical-experts/dr-pamela-mangat/rheumatoid-arthritis-expert-approach
RA Inflammatory Mediators
RA is primarily an inflammation of the joints with over-production of inflammatory mediators that cause damage in the joint itself. These mediators involve cytokines such as tumour necrosis factor (TNF). Therefore, inhibition of these mediators is the prime goal of biologics. Compared to traditional DMARDs, these agents can have a better control of inflammation and significantly improve RA symptoms.
Fighting Fire with Fire
The normal function of these mediators is central to a healthy immune system, so the theoretical trouble is that by interfering with the immune system by inhibiting these mediators, you could also render the patient more susceptible to infection and tumours (malignancy). In one large observational study involving 13,000 patients with RA, half of whom were treated with biologics, a small but significant increase in skin cancer was found. Also, some observational studies found an increased risk of lymphoma in patients with RA exposed to biologics, while other studies did not.
Are the Biologic Drugs Safe?
There does seem to be a good degree of conflicting evidence. One recent study including 74 RCTs evaluated cancer risk with TNF inhibitors used for any indication. A short-term risk for non-melanoma skin cancer was found, but there was no increased short-term risk for any other cancer. A limitation of this study was that ii was only a very short-term assessment.
The 2011 Cochrane Review did not conclude that there was an increased risk of malignancy due to biologics when compared to placebo/control treatment. However, the reactivation of tuberculosis was determined to be significantly more likely in the biologics group compared to control, so all patients should have a TB skin test before starting therapy.
The most recent big study into the use of biologics in RA patients included 63 separate trials, more than 29,000 patients followed for a minimum of 24 weeks. The number and type of malignancy was assessed at 24, 52, 104, and 156 weeks.
Of the 29,423 patients:
· 211 developed malignancy during the trial
· 23 in the biologic monotherapy group
· 123 in the biologic combination therapy group, and
· 65 in the control group.
There was no statistically significant increased risk of any type of cancer with the use of biologics as compared to controls. There was a small but significant increase in risk of malignancy at 52 weeks for patients on a combination of TNF inhibitors and methotrexate, but this was not found at the other time points.
However, scientists report that the clinical significance was questionable. Limitations of the study included a lack of detail and publication bias.
Though this recent study did not find cancer risk from biologics used in RA in the short term, more information is still needed. In his article for MedPageToday, Do Biologic Response Modifiers Used in RA Increase Risk of Malignancy? Sanjai Sinha, MD, Assistant Professor, Weill Cornell Medical College, New York says, “Observational studies are likely the only practical tool to continue the evaluation of the risk of malignancy from BRMs (biologic drugs). But for many RA patients, these biologic agents are a life-changing option, especially when used concomitantly with traditional DMARDs in early, moderately active RA.”