Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay

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Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay

A wide range of DMARDs is currently available for the treatment of RA. Once diagnosed, a combination of DMARD tablets is administered to the patient as a part of the initial treatment. These medications are especially effective in reducing the development of the symptoms of the condition thereby slowing down the progression of the disease. The medicine functions by blocking the harmful effects of the chemicals produced during the attack of the joints by the immune system. If left uncontrolled, the chemicals can cause extensive damage to the nearby tendons, bones, cartilage, and ligaments (NHS, 2014).

There are various DMARDs available for the treatment of RA. The available drugs include methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide. Methotrexate is the most frequently administered DMARD to patients with rheumatoid arthritis. The drug exhibits a rapid onset of action and is the most effective in this class of drugs. Methotrexate is commonly the first DMARD employed in the medication of RA in both children and adults (NHS, 2014). Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.

According to Smeltzer, Bare, Hinkle, and Cheever (2010), methotrexate primarily works by slowing down the effects of RA. Its use results in the decreased synovitis, less narrowing of the joint space, and decreased bone erosion. The medication inhibits folic acid synthesis, thereby inhibiting the proliferation of lymphocytes among other cells, eliciting autoimmune reactions in RA. Other inhibitory effects exerted by methotrexate include stimulation of adenosine release and inhibition of inflammatory cytokines. The suppression of adenosine release ensures the increased quantities of endogenous adenosine. The latter normally acts by inhibiting various mechanisms of the patient’s immune system (Ciconne, 2007).

The nurses should administer DMARD alongside a short-course of corticosteroids as a pain reliever due to the prolonged onset of action. The medication can also be combined with the biological treatments for the better results. Methotrexate is somewhat a toxic medicine, and certain side effects might occur that the nurses need to monitor. The principle problems associated with the drug involve the gastrointestinal tract. The effects include nausea, loss of appetite, sore mouth, diarrhea, and intra-gastrointestinal hemorrhage, among the other gastrointestinal distress. The prolonged use of methotrexate in the RA patients has also been associated with the hematologic disorders, pulmonary problems, hair loss, and liver dysfunction., The regular blood tests are essential to monitor its effects during the period of drug administration due to the effect of methotrexate on blood count (Ciconne, 2007).

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Occasionally, methotrexate can have negative effects on the lungs. Therefore, having a chest X-ray during administration of the drug is essential. The tests will enable the comparison if the patient develops persistent dry cough or experience shortness of breath while taking methotrexate (NHS, 2014). These adverse side effects often constrain the use of methotrexate in the treatment of RA. Most RA patients who discontinue the use of this methotrexate do so due to the adverse side effects. Rarely do patients stop taking the drug due to the loss of effectiveness. Nevertheless, most people tolerate the drug well. It offers an encouraging benefit-to-risk ratio in numerous rheumatoid arthritis patients in comparison to other DMARD medications (Ciconne, 2007).

The nurses should monitor patients receiving infliximab or abatacept for hypersensitivity reactions that might occur during and after IV fusion. Manifestations of lymphoma in patients on DMARDs should also be supervised. The nurses should as well put liver function and blood for patients on DMARDs, especially infliximab, under close supervision (Broyles, Reiss, & Evans, 2012).

Characteristically, it might last for a few months before the patient notices that a DMARD is working. Therefore, it is imperative for the patient to continue with the dose even if he/she does not notice methotrexate working at first (NHS, 2014). A patient might also need to try two or three types of DMARD before settling on the most suitable one. Once the patient and the doctor settle on the most suitable DMARD, the doctor will always advise the patient to take the medicine for a prolonged period (NHS, 2014).

Treatment during Pregnancy

Rheumatoid arthritis medication during pregnancy is often complex since none of the above-discussed drugs have been proven to be safe if administered to the pregnant women. Therefore, the medication decisions demand thoughtful consideration of the benefits and risks to both the fetus and the mother. It is prudent to stop all DMARD medication in pregnant and lactating women, and even in women planning to conceive. Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.Either there exist evidence of the risks that DMARDs pose to the fetus or possibility of their existence cannot be ignored. Hyrdoxychloroquine is perhaps the safest DMARD for administration during pregnancy. There is evidence of potential teratogenicity of methotrexate; the administration of the drug should be discontinued in both mothers and women planning conception. Leflunomide is teratogenic: therefore, women who have been on the drug and have been planning conception should undertake the washout of its chemicals (Johns Hopkins Center, 2014).

Though the safety of NSAIDs and prednisone are yet to be demonstrated, there is no evidence that these drugs pose threats to the fetus when administered in the first two trimesters. The joint symptoms control is best done with the lowest possible prednisone dose. Possible prednisone complications in pregnant women comprise hypertension, progression of maternal gestational diabetes, and retardation of intrauterine growth. The expecting patients ought to avoid NSAIDs in the third trimester due to the possibility of early closure of the ductus arteriosus, peripartum hemorrhage, and prolonged labor. Despite the excretion of NSAIDs and prednisone in the breast milk, the American Academy of Pediatrics considers both compatible with the breast-feeding (Johns Hopkins Center, 2014).

Conclusion

Rheumatoid arthritis is a joint disease that can generate overwhelming effects on the functioning, as well as structure, of the synovial joints. Fortuitously, the management of the complication can be improved considerably following the advancements of the drug therapy. Pharmacological treatment of the rheumatoid arthritis can be achieved through the administration of NSAIDs, various DMARDs, and glucocorticoids. NSAIDs represent the primary form of medication in the initial stages of RA. As the severity of the arthritic condition increases, the drugs are commonly administered in the conjunction with other drugs. Glucocorticoids are largely effective in the reduction of the joint inflammation, a condition typical of RA. Nonetheless, the administration of DMARDs is limited due to their toxic effects. DMARDs are often administered to halt or slow down the progression of RA. It acts by suppressing the immune response, a typical occurrence in RA. Although these medications are important, the pharmacological management of RA, in the long-term, is scarcely favorable. As a rule, the potential long-term benefit of these treatments is limited by the removal or withdrawal of patients from their prescribed course of treatment due to the adverse side effects. Nonetheless, combining pharmacological treatment with other modes of therapy such as physical exercise might prove more effective. Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.

References

Broyles, B., Reiss, B., & Evans, M. (2012). Pharmacological aspects of nursing. Boston, MA: Cengage Learning.
Ciccone, C. (2007). Pharmacology in rehabilitation (4th ed.). Philadelphia, PA: F.A. Davis Company.
Crouch, S., Crouch, M., & Chapelhow, C. (2008). Medicines management: A nursing perspective. London: Routledge.
Johns Hopkins Center. (2014). Rheumatoid arthritis treatment.
Lehne, R. (2013). Pharmacology for nursing care. St. Louis, MO: Elsevier/Saunders.
Management of rheumatoid arthritis. (2014). Patient.Co.UK.
NHS. (2014). Treating rheumatoid arthritis.
Newman, S., Fitzpatrick, R. Revenson, T., Skevington, S, & Williams, G. (1995). Understanding rheumatoid arthritis. London: Routledge.
Smeltzer, S., Bare, B., Hinkle, J. L., & Cheever, K. H. (2010). Brunner & Suddarth’s textbook of medical-surgical nursing (11th ed.). Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins.
Zychowicz, M. E. (Ed.). (2003). Orthopedic nursing secrets. Philadelphia, PA: Hanley & Belfus.

Disease-modifying antirheumatic drugs (DMARDs) are a class of drugs indicated for the treatment of inflammatory arthritides including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). They can also be used to in the treatment of other disorders including connective tissue disease such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Sjogren syndrome (SS), as well as in treatment of inflammatory myositis, vasculitis, uveitis, inflammatory bowel disease, and some types of cancers.[1][2][3] Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.

DMARDs are immunosuppressive and immunomodulatory agents and are classified as either conventional DMARDs or biologic DMARDs. Commonly used conventional DMARDs include methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine. Biologic DMARDs were introduced in the early 1990s and are usually prescribed after the failure of conventional DMARD therapy (ongoing disease activity, or clinical or radiographic disease progression). Some biologic agents include infliximab, adalimumab, etanercept, rituximab, abatacept, rituximab, tocilizumab, tofacitinib, among others. Biologic DMARDs are highly specific and target a specific pathway of the immune system. Some of these drugs are monoclonal chimeric humanized fusions antibodies, while others are receptors that have been fused to a part of the human immunoglobulin or small molecules such as Janus kinase (JAK) inhibitors.

DMARDs in rheumatoid arthritis

Although many medications can be used in the treatment of RA, methotrexate is the most commonly used agent as an initial treatment. RA treatment is complicated with several factors playing a role in decision making, including disease activity and severity, comorbidities, and patient preference (including cost, route of administration and frequency of monitoring). Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay. RA treatment can be either monotherapy or combination therapy, although several randomized controlled trials have shown the superiority of combination therapy of a biologic DMARD with a conventional DMARD such as methotrexate over either agent alone. Treatment goals shall include achieving remission or low disease activity, as well as prevent radiographic progression of the disease. The initiation of therapy early in the disease has shown to prevent radiographic progression, most of which occurs within the first few months of the disease.

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Mechanism of Action

Each DMARD has a unique mechanism of action ultimately interfering with critical pathways in the inflammatory cascade. Methotrexate, for example, stimulates adenosine release from fibroblasts, reduces neutrophil adhesion, inhibits leukotriene B4 synthesis by neutrophils, inhibits local IL-1 production, reduces levels of IL-6 and IL-8, suppresses cell-mediated immunity, and inhibits synovial collagenase gene expression. Other medications in this class serve to inhibit proliferation or cause dysfunction of lymphocytes. Leflunomide inhibits dihydroorotate dehydrogenase resulting in inhibition of pyrimidine synthesis hence blocking lymphocyte proliferation. Sulfasalazine mediates its anti-inflammatory effects by preventing oxidative, nitrative and nitrosative damage. Hydroxychloroquine, on the other hand, is a very mild immunomodulatory agent that inhibits intracellular toll-like receptor TLR9.

Biologics, on the other hand, are very selective in their mechanism of action. The overarching functions of biologics include (1) interfering with cytokine function or production, (2) inhibiting the “second signal” required for T-cell activation, or (3) depleting B-cells or inhibiting factors that active B-cells. Tofacitinib is a small molecule inhibitor of JAK, a protein tyrosine kinase involved in mediating cytokine signaling.[4][5]

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Administration

DMARDs (biologics and non-biologics) can be administered orally, subcutaneously (SC) or intravenously (IV). Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.

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Adverse Effects

Although most conventional DMARDs have similar adverse effects, there are several adverse effects unique to each agent.

Hydroxychloroquine is unique in this respect as it has the best safety profile out of all the conventional DMARDs. In comparison to other conventional DMARDs, hydroxychloroquine does not increase the risk of severe infections, nor does it cause hepatotoxicity or renal dysfunction. Common adverse effects of hydroxychloroquine include rash, diarrhea. A rare but significant adverse effect of hydroxychloroquine is retinopathy/maculopathy which is seen with a higher cumulative dose. Risk factors for hydroxychloroquine maculopathy include more than 5 mg/kg/day dose, more than 5 years of therapy, advancing age and chronic kidney disease. Patients on hydroxychloroquine are recommended to have regular ophthalmology evaluation with ocular coherence tomography which is a very sensitive test for maculopathy and can diagnose it well before visual field defects occur. Other rare adverse effects of hydroxychloroquine include anemia, leukopenia, myopathy, and cardiomyopathy.

Methotrexate, leflunomide, and sulfasalazine are similar in their adverse effect profile. Gastrointestinal distress (nausea, abdominal pain, diarrhea), rash/allergic reaction, bone marrow suppression, hepatotoxicity and higher incidence of common and sometimes serious infections are common adverse effects of all these agents. Both methotrexate and leflunomide can cause alopecia. Other adverse effects unique to methotrexate include interstitial lung disease, folic acid deficiency, and liver cirrhosis. Leflunomide can cause hypertension, peripheral neuropathy, and weight loss. Sulfasalazine has a very high risk of gastrointestinal distress. It can rarely cause DRESS syndrome as well.[6]

The most concerning adverse effect of all biologic DMARDs is increased risk of common and serious infections including bacterial, fungal and viral infections. Reactivation of tuberculosis, herpes zoster and hepatitis B/C can also occur. Rarely, bone marrow suppression and hepatotoxicity have been reported with biologic DMARDs. Anti TNF agents can cause worsening of severe congestive heart failure, drug-induced lupus, demyelinating central nervous system (CNS) diseases. Lymphomas and non-melanoma skin cancers may be associated with Anti-TNF agents as well. Hyperlipidemia, elevated liver function test and pancytopenia can be caused by IL-6 inhibitors and JAK inhibitors. Worsening of chronic obstructive airway disease has been reported secondary to abatacept. IL-17 inhibitors can cause/worsen inflammatory bowel disease.Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay. Progressive multifocal leukoencephalopathy has been reported in patients treated with rituximab.

Drug interactions

Several medications such as non-steroidal anti-inflammatory agents (NSAIDs), proton pump inhibitors, sulfasalazine, amoxicillin can interfere with renal excretion of methotrexate, hence increasing its efficacy, and also increasing the risk of adverse effects.

While the combination of a biologic DMARD with a conventional DMARD and the use of multiple conventional DMARDS is considered safe, it is not recommended to use a combination of different biologic DMARDs due to an increased risk of severe immunosuppression leading to severe and potentially life-threatening infections.

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Contraindications

DMARDs especially biologic DMARDs shall be avoided in patients who have an active infection, those with preexisting bone marrow hypoplasia, leukopenia, or immunodeficiency syndromes. Methotrexate and leflunomide shall be avoided in patients with severe liver disease.

Pregnancy and lactation

Methotrexate and leflunomide are contraindicated in pregnancy and lactation due to their teratogenic effects. Sulfasalazine can cause jaundice in the infant, especially if used in the third trimester of pregnancy and shall be used with caution in lactation. While hydroxychloroquine can cross the placenta, no cases of fetal ocular toxicity have been reported, and it is considered safe to be used in pregnancy and is actually strongly recommended to be used in pregnant females with systemic lupus erythematosus as it prevents flares of the disease in pregnancy.

There is limited safety data on the biologic DMARDs in pregnancy, although, of all biologics, certolizumab is the only one that does not cross placenta due to the larger size of the molecule, and is considered relatively safer to be used in pregnancy. Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.

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Monitoring

Prior to starting a DMARD, patients shall be screened for hepatitis B and C. Additionally, screening for tuberculosis is strongly recommended before initiating any biologic DMARD.[7][8][9]

Some of these agents are teratogenic, while safety has not been established in pregnancy for other agents. In women of childbearing age, pregnancy test shall be done before initiating these agents. Further, all women of childbearing age who are on these agents (especially methotrexate or leflunomide) shall be on appropriate contraception.

Myelosuppression and hepatotoxicity are more common early in therapy, although can occur at any time in a patient on a DMARD. Therefore, more frequent monitoring is recommended early in therapy and less frequent but regular monitoring shall be continued as long as the patient is on the DMARD once early safety has been established.

Complete blood count and liver function test shall be performed monthly for at least 3 months initially, and every 2-3 months thereafter in patients initiated on agents including methotrexate, leflunomide, sulfasalazine, tocilizumab, tofacitinib, and sarilumab.
Lipid panel shall be monitored at baseline and then every 3 months for at least 6 months and then every 6 months thereafter in patients initiated on tocilizumab, tofacitinib, and sarilumab.
CBC shall be monitored every 6 months in patients on any of the biologic DMARDs.
Since many of these agents require dose adjustment in renal insufficiency, close monitoring of renal function every 3 to 6 months is also recommended in patients on DMARDs.
Comprehensive ophthalmology exam including visual field testing and ocular coherence tomography shall be tested at baseline, at 5 years, and then annually in patients on hydroxychloroquine. Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.

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Toxicity

High dose methotrexate, especially when delivered intravenously in patients for treatment of some cancers can cause severe pancytopenia and transaminitis. In these cases, leucovorin rescue is used to terminate methotrexate toxicity.[10]

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Enhancing Healthcare Team Outcomes

Disease-modifying antirheumatic drugs (DMARDs) are a class of drugs indicated for the treatment of rheumatoid arthritis (RA) and many other autoimmune disorders including systemic sclerosis, vasculitis, spondyloarthritis, inflammatory myositis, inflammatory bowel disease, systemic lupus erythematosus, and some types of cancers. Due to the high complexity involved in the appropriate use of these agents, and monitoring for adverse effects, DMARDs shall be ideally prescribed by an appropriate specialist such as rheumatologist, gastroenterologist or dermatologist. The prescribing provider shall be familiar with these agents, their indications and adverse effects. All patients prescribed DMARDs need to be closely followed to monitor their effectiveness and side effects.

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Questions

To access free multiple choice questions on this topic, click here.

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References

1.: Gregori D, Giacovelli G, Minto C, Barbetta B, Gualtieri F, Azzolina D, Vaghi P, Rovati LC. Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. JAMA. 2018 Dec 25;320(24):2564-2579. [PMC free article] [PubMed]
2.: Lyseng-Williamson KA. Anakinra in Still’s disease: a profile of its use. Drugs Ther Perspect. 2018;34(12):543-553. [PMC free article] [PubMed] Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.
3.: Abbasi M, Mousavi MJ, Jamalzehi S, Alimohammadi R, Bezvan MH, Mohammadi H, Aslani S. Strategies toward rheumatoid arthritis therapy; the old and the new. J. Cell. Physiol. 2019 Jul;234(7):10018-10031. [PubMed]
4.: Aletaha D, Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA. 2018 Oct 02;320(13):1360-1372. [PubMed]
5.: Wang W, Zhou H, Liu L. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. Eur J Med Chem. 2018 Oct 05;158:502-516. [PubMed]
6.: Lian BS, Busmanis I, Lee HY. Relapsing Course of Sulfasalazine-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Complicated by Alopecia Universalis and Vitiligo. Ann. Acad. Med. Singap. 2018 Nov;47(11):492-493. [PubMed]
7.: Oo WM, Yu SP, Daniel MS, Hunter DJ. Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics. Expert Opin Emerg Drugs. 2018 Dec;23(4):331-347.[PubMed]
8.: Hughes CD, Scott DL, Ibrahim F., TITRATE Programme Investigators. Intensive therapy and remissions in rheumatoid arthritis: a systematic review. BMC Musculoskelet Disord. 2018 Oct 30;19(1):389. [PMC free article] [PubMed]
9.: Haraoui B, Jamal S, Ahluwalia V, Fung D, Manchanda T, Khraishi M. Real-World Tocilizumab Use in Patients with Rheumatoid Arthritis in Canada: 12-Month Results From an Observational, Noninterventional Study. Rheumatol Ther. 2018 Dec;5(2):551-565. [PMC free article] [PubMed]
10.: Hegde VS, Nagalli S. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Apr 28, 2020. Leucovorin. [PubMed] Disease-Modifying Anti-rheumatic Drugs (DMARDs) Essay.