First, we will mention Rheumatoid Arthritis (RA) because the first biologic launched to the market was directed to treat this disease. Multiple factors cause RA, but once the diagnosis is established is crucial to start treating these patients as soon as possible, to induce the remission of the disease. Until the past century in the therapeutic armamentarium we had few drugs to treat RA. All, were chemical compounds like NSAIDS, corticosteroids, gold salts (now withdrawn from the market because of their side effects), hydroxychloroquine, sulfasalazine, leflunomide and Methotrexate (MTX), which, has become the gold standard to treat the disease. However, not all patients (30-50%) respond to these meds and the disease progresses gradually towards a significant disability. Therefore at the end of the twentieth century, the possibility of producing other, more complex drugs was devised. These new drugs are call biologics since they are not chemical formulations,
They are complex proteins, mainly monoclonal antibodies, that block other proteins (called cytokines) involved in inflammation in RA. One of the most prominent pro-inflammatory cytokines is TNF. Therefore, the first biologics were designed to block TNF.
Distintos Biológicos para la AR
See below the anti-TNF that are in the pharmaceutical market (in brackets the commercial name)
- Infliximab, IV administration (Remicade®). Now we have two infliximab-biosimilar products in Europe, and in some other countries called Remsima® and Inflectra® (in another section I will explain what means a biosimilar drug)
- Etanercept weekly subcutaneous administration (Enbrel®)
- Adalimumab, biweekly subcutaneous administration (Humira®)
- Certolizumab, biweekly subcutaneous administration (Cimzia®)
- Golimumab monthly subcutaneous administration (Simponi®)
Biologics non anti-TNF
Apart TNF, interleukin 6 (IL-6) is another cytokine involved in inflammation. Tocilizumab (RoActemra®) is the first anti-IL-6 approved to treat RA. Tocilizumab is administered IV monthly but recently a subcutaneous formulation has been launched.
Interestingly, a biologic that years ago was used to treat non-Hodgkin lymphoma -Rituximab- was shown to be useful in RA. Rituximab is administered IV at least once every six months. (Mabthera®). This biologic acts against B lymphocytes, which are responsible for producing antibodies.
Finally, another relevant biologic is Abatacept (Orencia®). Abatacept interferes with the contact between the interaction of two types of lymphocytes (T and B) that are essential for the harmful effects of the disease occur. Abatacept has an IV presentation but recently a subcutaneous presentation is in the market.
Ankylosing Spondylitis (AS)
For AS, only anti-TNF have been shown to be effective and have been licensed to treat the disease. Other promising drugs are under development, but it may take a few years to have other biologics to treat this disease
Psoriatic Arthritis PsA
Until recently only anti-TNF had been licensed to treat this disease. Recently, a new non anti-TNF biologic Ustekinumab (Stelara®) has been approved to treat PsA. Ustekinumab was launched first for cutaneous psoriasis, but it took a while to demonstrate that it was also efficacious in PsA.