Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affect typically more than just your joints. Rheumatoid arthritis is often associated with symptoms from other organs including the skin, eyes, lungs, heart and blood vessels.

Rheumatoid Arthritis is an autoimmune disorder, ie a disease caused by unwanted activity in the immune system, where the immune system mistakenly attacks your own body’s tissues.

Rheumatoid arthritis affects the lining of the joints, causing a painful swelling that can eventually result in bone erosion and joint deformity.

The inflammation associated with rheumatoid arthritis is what can damage other parts of the body as well.

While new types of medications have improved treatment options dramatically, severe rheumatoid arthritis can still cause physical disabilities.

Medical treatment of RA depends of the severity of the disease

First line treatment is Nonsteroidal anti-inflammatory drugs (NSAIDs). These compounds can relieve pain and reduce inflammation. Side effects associated to NSAID treatment includes stomach irritation and affection of kidney function.

Severe symptoms can be treated with Glucocorticoids (also called Steroids). Corticosteroids as prednisolone reduce inflammation and pain and slow joint damage. Unfortunately, continued treatment with Glucocorticoids is associated with treatment limiting side effects that includes (but limited to) thinning of bones, weight gain and diabetes. Treatment with Glucocorticioids is therefore limited to short term treatment to relieve acute symptoms. Recently intra-articular administration of Glucocorticoids has been introduced as an effective treatment for acute relief. However, intra-articular administration is time consuming and associated with (even low) risk for local infections.

If symptoms can not be controlled by NSAID, Disease-modifying antirheumatic drugs (DMARDs) will be applied. These drugs can slow the progression of RA and save the joints and other tissues from permanent damage. First choice DMARD treatment is typically methotrexate. Examples of other DMARDS are leflunomide, hydroxychloroquine and sulfasalazine. DMARD treatment is associated to a number of severe side effects that includes liver damage, bone marrow suppression and severe lung infections. For that reason treatments with DMARD has to been given in a controlled way, often by use of dose escalation and tight monitoring of signs of adverse events. For MTX treatment, as an example, toxic levels and even fatal levels of the compound can be reached if the patients misunderstand the dose regiment and take the medicine on a daily and not weekly basis. Nevertheless, MTX is first choice treatment in most patients and will in up to 60% of the patient’s results is disease control. For the remainders, often referred to as inappropriate MTX responders, addition therapy has to be applied.

Biologic agents, alternatively called biologic response modifiers, is a relatively new class of DMARDs that includes abatacept, adalimumab, anakinra, baricitinib, certolizumab, etanercept, golimumab, infliximab, rituximab, sarilumab, tocilizumab and tofacitinib among other. The compound target specific pathways in the immune system who trigger inflammation that causes joint and tissue damage. Biologic agents are often very effective, but the use of the compound has also identified that RA is not one, but a whole range of diseases that all present with affection the joints. The reason is that one specific compound aimed to block a specific inflammatory pathway work very well in some patients, but has no effect on other patients. This means that it often is needed to try treatment with more than one biologic agent in order get an optimal treatment effect. Another issue related to the biologic agents is that they are associated with increased risk for unwanted and treatment limiting infections- In addition it has been suggested that long term treatment with some biologic agents is associated with increased risk for malignancy. Biologic agents will typically be given as add on to non-biologic DMARDs as MTX.

Recently a new type of oral available compounds, called JAK2 inhibitors has been introduced for treatment of RA. The compounds seem to be effective, but unfortunately the compounds are as the DMARDs associated with increased risk for treatment limiting infections.

New compound that will reduce the need for high dose treatment with DMARD both the non-biologic as MTX as well as the biologic agents, that can induce disease remission without increasing the risk for unwanted infections is high on the list in today’s medicine. That why resolution therapy, with the potential to induce disease remission without concomitant immune-suppression and thereby increased risk for infections, would be an attractive new treatment modality in RA and other inflammatory and auto-immune diseases.