Do the new Biologic Drugs including anti-TNF’s for Rheumatoid Arthritis (RA) increase risk of cancer and infection?

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 -

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.”

Inflammation of one or more joints of the body. Full medical glossary
Abnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. Full medical glossary
The abbreviation for computed tomography, a scan that generates a series of cross-sectional x-ray images Full medical glossary
An abbreviation for diabetes mellitus. Full medical glossary
The organs specialised to fight infection. Full medical glossary
Invasion by organisms that may be harmful, for example bacteria or parasites. Full medical glossary
The body’s response to injury. Full medical glossary
A watery or milky bodily fluid containing lymphocytes, proteins and fats. Lymph accumulates outside the blood vessels in the intercellular spaces of the body tiisues and is collected by the vessels of the lymphatic system. Full medical glossary
A type of cancer that affects the lymph nodes, part of the immune system. Full medical glossary
A malignant tumour arising from pigmented cells or melanocytes, most often in the skin Full medical glossary
Relating to the skeleton and its attached muscles, cartilage, tendons and ligaments that gives structure to the body and enables movement Full medical glossary
Death of cells or tissue in the body due to disease, injury or impaired blood supply. Full medical glossary
rheumatoid arthritis Full medical glossary
Randomised controlled trial. A study comparing the outcomes between one or more different treatments for a disease (or in some instances, preventive measures against that disease) and no active treatment at all (the placebo group). Study participants are allocated to the various groups on a random basis. Full medical glossary
The lessening or disappearance of the symptoms or signs of a disease. Full medical glossary
The abbreviation for tuberculosis, an infectious disease. Full medical glossary
trigeminal neuralgia Full medical glossary
An abbreviation for tumour necrosis factor, a protein that stimulates inflammation and causes cells to die. Full medical glossary
An infectious disease caused by the bacterium Mycobacterium Tuberculosis. Full medical glossary
An abnormal swelling. Full medical glossary