Disease-Modifying Antirheumatic Drug - An Overview

Introduction

Disease-modifying antirheumatic drugs (DMARDs) are medications primarily used to treat rheumatoid arthritis, effectively reducing inflammation, pain, tissue damage, and disease progression. This group encompasses both traditional DMARDs and newer biological options that specifically target the disease. The treatment plan will involve regular checkups to assess progress and monitor potential side effects.

What Are the Indications of Disease-Modifying Antirheumatic Drugs?

Disease-modifying antirheumatic drugs (DMARDs) are a category of medications used to treat various conditions characterized by inflammation and immune system dysfunction, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and other autoimmune diseases like systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Sjogren syndrome (SS). They can also be employed in managing inflammatory myositis, vasculitis, uveitis, inflammatory bowel disease, and certain types of cancers.

• DMARDs are divided into two main types: conventional DMARDs and biologic DMARDs. Conventional DMARDs include well-known drugs like Methotrexate, Leflunomide, Hydroxychloroquine, and Sulfasalazine.

• Biologic DMARDs, introduced in the 1990s, are typically prescribed when conventional DMARDs prove insufficient in controlling the disease.

  • Biologics include agents like Infliximab, Adalimumab, Etanercept, Rituximab, Abatacept, Tocilizumab, and Tofacitinib, among others.

  • These biologic DMARDs are highly specific and target particular aspects of the immune system. Some are monoclonal antibodies, while others are receptors fused with parts of human immunoglobulins or small molecules like Janus kinase (JAK) inhibitors.

In the case of rheumatoid arthritis (RA), Methotrexate is often the first-line treatment. The management of RA can be complex, with several factors influencing treatment decisions, including the severity of the disease, any other health conditions the patient may have, and their preferences regarding factors such as cost, method of administration, and monitoring frequency. Treatment for RA can involve a single DMARD or a combination of them. Research has shown that combining a biological DMARD with a conventional DMARD like Methotrexate is often more effective than using either drug alone. The primary treatment goals are to achieve remission or low disease activity and to prevent the progression of joint damage. Starting treatment early in the course of the disease is crucial to prevent long-term joint damage, which often occurs within the first few months of disease onset.

How Does a Disease-Modifying Antirheumatic Drug Work?

Each DMARD (Disease-Modifying Antirheumatic Drug) works in its own unique way to fight inflammation and manage diseases like arthritis. For instance, Methotrexate does various things like reducing inflammation signals, suppressing the immune system, and preventing damage to joints. Leflunomide blocks a process that helps immune cells multiply. Sulfasalazine prevents certain types of damage caused by inflammation, and Hydroxychloroquine mildly changes how the immune system works. Biologics, on the other hand, are very specific in how they work. They mainly do three things:

• Mess with signals that cause inflammation.

• Stop the activation of immune cells.

• Reduce or block certain immune cells.

For example, Tofacitinib is a small drug that targets a specific protein involved in inflammation signaling.

How Are DMARDs Taken?

Conventional DMARDs are typically taken orally (by mouth), while biologic DMARDs are administered through injections or infusions into a vein. However, Janus kinase inhibitor biologics are an exception, as they are available in pill form and can be taken orally.

What Are the DMARDs’ Adverse Reactions?

Certainly, here are the key points regarding the adverse effects of DMARDs, both conventional and biological:

Conventional DMARDs:

• Hydroxychloroquine: Generally considered the safest conventional DMARD.

  • Rare risk of retinopathy (eye condition) with higher cumulative doses.

  • Possible Adverse Effects: Rash, diarrhea, anemia (low red blood cell count), leukopenia (low white blood cell count), myopathy (muscle disease), and cardiomyopathy (heart muscle disease).

• Methotrexate, Leflunomide, and Sulfasalazine: These drugs share common adverse effects.

  • Gastrointestinal distress (nausea, abdominal pain, diarrhea).

  • Rash or allergic reactions.

  • Bone marrow suppression.

  • Hepatotoxicity.

There is a higher risk of common and sometimes serious infections.

• Methotrexate-Specific Effects: Interstitial lung disease (lung tissue scarring), folic acid deficiency, liver cirrhosis (advanced liver scarring).

• Leflunomide-Specific Effects: Hypertension, peripheral neuropathy (nerve damage), weight loss.

• Sulfasalazine-Specific Effects: High risk of gastrointestinal distress and rare DRESS syndrome (Drug reaction with eosinophilia and systemic symptoms - a severe drug reaction that involves skin rash, fever, and inflammation of internal organs, often caused by medications).

Biologic DMARDs:

• General Adverse Effects:

  • Increased risk of common and serious infections (bacterial, fungal, viral).

  • Possible reactivation of tuberculosis, herpes zoster, hepatitis B or C.

  • Rare reports of bone marrow suppression and hepatotoxicity.

• Anti-TNF Agents:

  • It can worsen severe congestive heart failure.

  • Risk of drug-induced lupus, demyelinating central nervous system diseases.

  • Association with lymphomas and non-melanoma skin cancers.

• IL-6 Inhibitors and JAK Inhibitors: Adverse effects may include hyperlipidemia, elevated liver function tests, and pancytopenia.

• Abatacept: Linked to worsening of chronic obstructive airway disease.

• IL-17 Inhibitors: Can cause or worsen inflammatory bowel disease.

• Rituximab: Reported cases of progressive multifocal leukoencephalopathy (brain infection).

Drug Interactions:

Certain medications like NSAIDs, proton pump inhibitors, Sulfasalazine, and Amoxicillin can affect how Methotrexate works and increase its side effects.

Combination Therapy:

Combining a biologic DMARD with a conventional DMARD is generally considered safe.

However, using different biological DMARDs together is not recommended as it can lead to severe immunosuppression and potentially life-threatening infections.

What Are the Contraindications of DMARD?

Avoid DMARDs, especially biological ones, if they have an ongoing infection, bone marrow problems, low white blood cell count, or a weakened immune system. Methotrexate and Leflunomide should not be used if the individual has severe liver disease.

• Pregnancy and Breastfeeding:

  • Methotrexate and Leflunomide are not safe during pregnancy or breastfeeding because they can harm the baby.

  • Sulfasalazine might cause jaundice in the baby, so use it cautiously during breastfeeding.

  • Hydroxychloroquine is usually safe during pregnancy and is recommended for pregnant women with lupus as it helps prevent disease flare-ups.

  • There is limited data on the safety of biologic DMARDs during pregnancy, but Certolizumab is considered relatively safer because it does not cross the placenta to affect the baby.

What Safety Precautions and Monitoring Are Necessary When Taking DMARDs?

The important points about safety and monitoring when taking DMARDs are:

• Before Starting DMARDs:

  • Patients should be screened for hepatitis B and C before starting any DMARD.

  • Screening for tuberculosis is strongly recommended before beginning biologic DMARDs.

  • In women of childbearing age, a pregnancy test should be done before starting these medications.

  • Women of childbearing age, especially those on Methotrexate or Leflunomide, must use proper contraception.

• Monitoring Early in Treatment:

  • Myelosuppression (reduced blood cell production) and liver problems can happen, especially early in DMARD therapy.

  • Therefore, more frequent monitoring is needed at the beginning of treatment to ensure safety.

• Monitoring Specifics: For some DMARDs like Methotrexate, Leflunomide, Sulfasalazine, Tocilizumab, Tofacitinib, and Sarilumab:

  • Complete blood count (CBC) and liver function tests should be done monthly for at least three months initially and every two to three months afterward.

  • Lipid (cholesterol) levels should be checked at the start and then every three months for at least six months and then every six months afterward.

  • For biologic DMARDs, a CBC should be monitored every six months.

  • Kidney function should be checked every three to six months in patients taking DMARDs.

  • If one is on Hydroxychloroquine, comprehensive eye exams, including visual field testing and ocular coherence tomography, are needed at the beginning, at five years, and then annually to watch for eye problems.

Conclusion

DMARDs are medications used to treat various autoimmune disorders, including rheumatoid arthritis. The healthcare provider will help the patient choose the most suitable DMARD for their condition. Each DMARD has its unique side effects that require close monitoring. The provider may adjust the dose, switch to a different DMARD, or combine multiple DMARDs in the patient's treatment plan. Patients should not hesitate to ask their provider about the specific side effects associated with the prescribed DMARD and what to be aware of as they start their treatment with it.