Naturally, our immune system protects our body against environmental pathogens such as bacteria and viruses as well as against endogenous cells, which are functionally impaired. In autoimmune diseases, the immune-system recognizes the body’s own tissues as foreign and combats them. An excessive pathogenic immune-response results and leads to chronic inflammation. In rheumatoid arthritis (RA), this chronic inflammation affects mostly joints, but sometimes also other organs such as the lung.
Biologic disease modifying antirheumatic drugs (DMARDs) block endogenous messengers or cells that mediate auto-inflammation. Thereby, biologic DMARDs inhibit the rheumatic inflammation. Since the same messengers and cells play key roles in the defence against infections, the therapy with biologic DMARDs was assumed to be associated with a higher risk of severe infectious diseases. This risk was investigated in RABBIT for biologic agents that inhibit tumour-necrosis-factor-alpha (TNF-a) as one of the essential messengers of the rheumatic inflammation. TNF-a inhibitors are adalimumab (Humira®), certolizumab pegol (Cimzia®), etanercept (Enbrel®), golimumab (Simponi®), and infliximab (Remicade ®).
RABBIT data showed that treatment with TNF-a inhibitors exhibit a 1.5 times higher risk of infections compared to treatment with non-biologic DMARDs. However, this risk should not be evaluated separately, but has to be considered in the context with several other risk factors: Patients of higher age are at higher risk of infection than younger patients; the same is true for patients with chronic comorbidities compared to otherwise healthy patients, and for patients with highly active RA compared to patients with less active disease. Furthermore, history of severe infections and treatment with glucocorticoids come along with an increased infection risk. If disease activity can be decreased in a sustained manner and glucocorticoids can thereby be tapered down, the risk of infection may even be lower under biologic DMARDs than under non-biologic DMARDs. Using RABBIT data, a risk score was developed with which the individual risk for a patient to develop a severe infection within the next twelve months either under biologic or non-biologic DMARDs can be calculated (Strangfeld et al. Ann Rheum Dis. 2011; 70 (11): 1914-1920).