Rheumatoid arthritis: the new selective bioweapons and inhibitors

– evolution and trend according to the latest research progress.

Among the physically disabling diseases, rheumatoid arthritis is certainly one of the worst. From the notoriously self-immune nature, this pathology recognizes in its etiological basis an aggression of the immune system towards the symmetrical articular structures, then hands, feet and knees specifically. This justifies its highly disabling nature, although it can also affect synovias and muscle tendons or even internal organs. Its real etiopathogenesis is multifactorial: it is believed that cigarette smoking, wrong behavioral habits, specific viral infections (herpes virus and mononucleosis), together with a specific biological or genetic medium, can contribute to its appearance. The most recent microbiological hypotheses could see the contest of poor oral hygiene (periodontitis). Compared to classical and more frequent joint arthritis, rheumatoid arthritis is characterized by morning pain and stiffness, which worsens with physical activity. The joints are also swollen, as well as painful, and the chronicity of the disease leads to joint deformities that very rarely appear even in the most severe forms of generalized arthrosis. There are also lack of appetite with weight loss and muscle reduction. unlike osteoarthritis, fever is typical of the disease. The signs and symptoms of the disease may have a classic “poussè” pattern, that is, with acute, very painful and / or disabling phases that can occur in periods that are almost completely free of disturbances.

This behavior can be found in two other auto-immune diseases such as multiple sclerosis and Chron’s disease, indicating that there may be a common biological trend that intrinsically forms part of the natural history of these diseases. The battle against rheumatoid arthritis is essentially pharmacological and physiotherapeutic complement. The elimination of extreme habits (strong smoking and / alcohol abuse), a lifestyle that is definitely free of recurrent abuses or foods with low nutritional value are also recommended. Apart from the intervention of the cytokines of the immune system, in fact, oxidative stress is a scientifically proven fact in the AR. It would be a good idea, indeed, to direct one’s diet towards an anti-inflammatory and antioxidant background, such as dark fruit and vegetables, fish as an excellent source of omega-3 fatty acids and the reduction of flour and bakery products ( indirect antigenic action). Likewise, external supplements with polyphenols, antioxidant vitamins (for example, the classic A-C-E combination), microelements such as selenium, manganese and zinc and other antioxidants, in the form of plant extracts or individual molecules, are not discouraged at all. The intervention of free radicals in AR is both direct (possibly damaging) and indirect, ie consequential to inflammation and the action of the immune system’s cytokines. Therefore, targeted nutrition, associated or not with additional supplementation, can partially cope with the course of the disease.

The cardinal drugs of treatment were classically cortisone, due to their simultaneous anti-inflammatory and immunosuppressive action. The methotrexate, anti-folic and immmuno-suppressive drug, is cyclically taken for its anemic action. In case of refractory nature of these therapies, the so-called “course modifying drugs or DMARDs” have been used. These include chloroquine (Plaquenil), sulfasalazine (Salazopyrin), leflunomide (Arava) and iguratimod (Careram). They are not directly immunosuppressive drugs, but modulate some immune and inflammatory responses that do not enhance a counter-response of lymphocytes, which have become refractory to the classic drug. Today, given the serious side effects that accompany their chronic intake, these drugs are used less and less or otherwise, mono-therapy is absolutely not recommended. We tend to associate at least two drugs, which greatly modifies the appearance of side effects. Biological therapies based on monoclonal antibodies against cytokines are also available. One of the most recent is mavrilimumab, directed against the GM-CSF protein and which has just entered a phase 2 controlled clinical trial (Burmester et al., 2017), the other is tocilizumab, which has been successfully released from a 12-month single-therapeutic trial (Flipo RM et al, 2017).

Finally, there is abatacept, an immunoglobulin directed against cytotoxic T lymphocytes, the cells that directly destroy the joints. Its use is reserved for cases resistant to leflunomide and methotrexate. A very last hope seems to come from the baricitinib (Olumiant), a selective inhibitor of JAK1 and JAK2 proteins. It is a member of the family of the so-called INIBS molecules (for more information, read the article on the site “Farewell chemo: welcome inhibs”). Baricitinib is the third member, after tofacitinib (Xeljanz) and ruxolitinib (Jakavi), two other inhibitors of JAKs that have been approved for myelodysplasia, psoriasis, aerated alopecia and rheumatoid arthritis. Within the immune cells, JAKs mediate the signal of many cytokines, including those involved in rheumatoid arthritis (IL-1, IL-6, GM-CSF, TNF-alpha). In this way, the drug does not only act as an immunosuppressant, but also as an indirect anti-inflammatory agent. In 2016, the FDA authorized the pharmaceutical company Eli-Lilly to initiate treatments with baricitinib for patients with AR forms particularly severe and / or resistant even to biological therapies.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochiemistry.

References within

Burmester GR et al. (2017) Ann Rheum Dis, Feb 2017.

Dougados M et al. (2017) An Rheum Dis.76(4): 694-700.

Flipo RM et al. (2017) RMD Open 3(1): e000340.

Gras J (2017) Drugs Today (Barc,) 52(10): 543-550.

Kim SC et al. (2017) Arthritis Reumatol. 10/2002: art.40084.

Kuryia B et al. (2017) Ther Adv Musculoskel Dis 9(2): 37-44.

Lopez-Millan B et al. (2017) Exp Mol Med 49(2): e920.

Informazioni su Dott. Gianfrancesco Cormaci 2484 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it