Rheumatoid Arthritis and Treatment

Rheumatoid Arthritis: Risks/Benefits of Latest Treatments

Rheumatoid arthritis (RA) is a form of arthritis characterized by swelling and tenderness which recent studies have revealed that approximately 1% of grownups suffer from. A common symptom of this disease is symmetric polyarticular inflammation of the synovium, typically of the small joints of the hands (MCP and PIP), wrists and feet. This swelling causes discomfort and difficulty of movement and could result into gradual joint injury characterized by misshapenness and disability. The major compound used in treating this rheumatoid arthritis (RA) is methotrexate. This compound has been used for over 40 years in treating various types of rheumatoid ailments and is still one of the most effective treatment methods for RA. Its combination with modern treatments which tackle the disorders in the immune system, conditions termed as biological DMARDs, have transformed the method of treating RA. This review will give a brief and succinct analysis of the dangers and value of the various therapies for rheumatoid ailments, with emphasis on Rheumatoid Arthritis.

Literature Review

Bird & Littlejohn in 2014 discovered that the earliest documented application of Methotrexate (MTX) was unobserved and overlooked but that was the day MTX started its journey to becoming a widely accepted modern day medication for rheumatic ailments. This journey from obscurity to prominence took MTX the best part of thirty years; however, it finally became the everyday treatment for rheumatic ailments. The exact method MTX employs in healing rheumatic diseases remains a puzzle. The most common belief happens to be that MTX inhibits de novo pyrimidine and purine synthesis, and as a result stops lymphocyte proliferation. Other presumed methods are higher apoptosis of T. cells, modification of manifestation of cellular adhesion molecules, surge in release of the endogenous anti-inflammatory adenosine, drop in expression of cellular adhesion molecules and anti-angiogenesis effects via indirect mechanisms such as disturbance of macrophage interaction (Bird & Littlejohn, 2014)

The effectiveness of MTX in treating RA is undisputed. As well as lessening the signs and symptoms of RA, it also stops the advancement of joint injury, enhances healthy living and reduces death rates. Curiously, combining MTX therapy with anti-TNF substances have been proved to have greater positive effects than applying anti-TNF substances alone. This discovery strengthens the belief that despite new technologies developed to treat RA, MTX still remains an important treatment for a large number of patients (Bird & Littlejohn, 2014).

Certain concerns have been identified over the safety of MTX use in treating rheumatic disease and these concerns are stated below in a risk-benefit analysis method.

Neurological

Psychological side effects of MTX include exhaustion, headaches and reduced alertness. These secondary effects may regulate treatment acceleration and can be reduced by augmentation with folic acid pills (Bird & Littlejohn, 2014).

Gastrointestinal

The most evident side effects from this group include mucositis, mouth ulceration, nausea and diarrhea. They do not occur frequently due to their prevention by proper use of folic acid supplements and are cured by cutting back or outright stopping of medication (Bird & Littlejohn, 2014)

Hepatotoxicity

Weekly usage of small amounts of MTX could have adverse side effects on the liver with reversible transaminase elevation, liver fibrosis and liver cirrhosis, the most commonly recorded side effects. In practice, however, reversible transaminase elevation is mostly recorded while fibrosis and cirrhosis are quite rarely seen greatly due to their identified precursors of excess alcohol intake or previous liver ailment. Patients on low dose of MTX are compulsorily monitored for transaminase levels and reduction or termination decisions are made based on the extent of transaminase increase (Bird & Littlejohn, 2014).

Pulmonary Abnormalities

Another very rare side effect (0.08% of treated patients) is lung disease which could occur in patients on either MTX treatments only or on MTX treatments combined with other medications. Other conditions that add to the tendency of MTX-induced lung damage are preexisting interstitial lung diseases (ILD), cigarette smoking, and low body weight (Bird & Littlejohn, 2014).

Small weekly prescriptions of MTX give effective, low-cost and widely accepted treatment for RA. Medical personnel, however, must be well versed on the dangers related to its administration and keep them in check (Bird & Littlejohn, 2014).

In 2011, Fox & Kahlenberg stated that in the past twenty years, the therapy mechanisms for RA have been modernized by new knowledge about the workings of its systemic procedures and the innovation of substances which tackles these procedures. These latest drugs have proved to be very effective in enhancing treatment efficiency but they are also associated with certain secondary effects which could cause lasting therapy problems and complexities when operations are necessary (Kahlenberg & Fox, 2011)

RA is a well-known ailment accustomed to general joint damage and problems resulting to swelling and tenderness. New therapy methods developed based on advanced knowledge of diseases have resulted to massive revolutions in the treatment of this disease. The insistent application of DMARD and biological DMARD treatments have brought about encouraging signs like easier limb use and reduced joint damage. However, these drugs also come with certain side effects and lasting consequences. A deep understanding of these downsides accompanied by this treatment will ensure the best treatment possible in either the medical and surgical situations (Kahlenberg & Fox, 2011)

Biologic DMARDs

The development of drugs aimed at tackling certain disorders of the immune system called the biological DMARDs have transformed the therapy for RA. These drugs whose numbers are constantly growing affects certain sites which have been proved to have effects on the mechanism of RA. Due to their costly nature and unpleasant secondary effects, their use is normally prescribed after normal single or combined DMARD treatments fail (Kahlenberg & Fox, 2011)

Another lately sanctioned biological treatment for medium to serious RA is called Tocilizumab. It is a recombinant humanized monoclonal antibody that binds to the IL-6 receptor where IL-6 is a pro inflammatory cytokine that is increased in the serum of the RA patients. Monthly doses of tocilizumab enhance limb use and general well-being while reducing advancement of RA in sufferers on whom traditional DMARDs and anti-TNF treatments have failed (Kahlenberg & Fox, 2011). The influence of tocilizumab is higher when combined with methotrexate-33. Its special system of fighting RA is now accompanied, however, by a greater danger of increased liver fluids and a controllable increase in cholesterol and triglycerides, thus only a carefully selected group of patients should be allowed to undergo this treatment. Transient neutropenia and thrombocytopenia have been noticed in 1 -- 3% of patients after taking this drug as well as intestinal tears (Kahlenberg & Fox, 2011).

RA on its own brings about a higher danger of diseases but this danger is significantly increased by DMARD and biologic therapies which repress the immune system. Tendency of contracting diseases caused by bacteria such as pneumonia are increased by the application of methotrexate and combining it with anti-TNF medication causes a 200 -- 400% rise of this risk. Biological DMARDs are not left out as their use also poses a risk of infection. Specifically, a huge tendency of recurrence of tuberculosis has been discovered to be related to anti-TNF therapy (Kahlenberg & Fox, 2011).

Singh et al. (2015) state that lots of sufferers seeking cures to rheumatoid arthritis are often worried of the threat of serious diseases. There has been no confirmation that biological medication carries a greater danger of acute infections when compared with normal disease-modifying anti rheumatic drugs (DMARDs). A systematic study and examination of acute infections in sufferers of RA placed on biological drugs in comparison with those placed on conventional DMARD therapy was carried out (Singh, et al., 2015).

The review recognized 106 cases, where acute illnesses were discovered, and patients with RA who had been treated with biological medication made up this number. Compared with traditional DMARDs, patients on standard-dose biological drugs (OR 1•31, 95% credible interval [Cri] 1•09 -- 1•58) as well as those on high-dose biological drugs (1•90, 1•50 -- 2•39) were discovered to exhibit a higher risk of acute infections, although patients placed on low-dose biological drugs (0•93, 0•65 -- 1•33) were not. Equally, the danger was also discovered to be low in sufferers who applied methotrexate treatments when compared with others who were on conventional DMARD treatments based on anti-tumor necrosis factor biological medications. From the review, an increase was noticed in the number of acute illnesses per 1000 sufferers who underwent therapy every year from 6 for those on normal biological medications to 55 for those on combined biological treatments, when compared with sufferers on traditional DMARDs (Singh, et al., 2015).