Introduction

DMARDs are disease-modifying anti-rheumatic drugs used to treat rheumatoid arthritis. Here, we review DMARDs pharmacology – the primary members, how they work and what indications they are used to treat.

Even though DMARDs share a common indication – rheumatoid arthritis – individual DMARDs are used to treat a variety of other inflammatory and auto-immune diseases. Below, we review the indications that each medicine is used to treat.

The purpose of DMARDs is clear – to slow progression of rheumatoid arthritis.

In contrast, NSAIDs – non-steroidal anti-inflammatory drugs – are used to treat inflammation but do not address the fundamental cause. DMARDs are used to address the cause and therefore slow disease progression. DMARDs also differ from steroid drugs, too. Steroids dampen the immune response, but do not address the underlying cause of the inflammatory state.

DMARDs are, then, an important clinical alternative.

DMARDs Classification

DMARDs pharmacology is commonly classified as follows:

  • Synthetic DMARDs (sDMARD)
  • Conventional synthetic (csDMARD): hydroxychloroquine, methotrexate; the traditional examples of DMARDs.
  • Targeted synthetic (tsDMARD): drugs developed with the purpose of targeting a specific molecular structure.
  • Biological DMARDs: modern drugs developed through genetic engineering.

Synthetic DMARDs are traditional, small molecular mass drugs in contrast to the heavier molecular mass biologic agents.

Of course, DMARDs are not only used to treat rheumatoid arthritis.

Due to their mechanism of action, DMARDs are effective in the treatment of other inflammatory-autoimmune states.

Examples include:

  • Crohn’s disease
  • Ankylosing spondylitis
  • Psoriatic arthritis
  • Systemic lupus erythematosus (SLE)
  • Sarcoidosis
  • Immune thrombocytopenic purpura (ITP)
  • Sjögren syndrome

The function of DMARDs is to reduce pain and inflammation; to prevent long-term joint damage; and to preserve the structure and function of bone/joints. This is achieved by suppressing the immune response / inflammatory reaction.

However, effects can take many weeks/months to take effect – depending on the drug, the patient, their condition, and disease progression:

  • Methotrexate – 6-8 weeks
  • Hydroxychloroquine – 2-4 months
  • Leflunomide – 4-8 weeks
  • Sulfasalazine – 6 weeks to 3 months
  • Abatacept – 3 months
  • Rituximab – 3 months
  • Tocilizumab – 4-8 weeks

DMARDs are not administered to provide immediate symptomatic relief. Other drugs, such as NSAIDs or analgesics, may instead be given for this purpose.

For this reason, DMARDs are sometimes referred to as “remission inducing drugs”.

Choosing the Right DMARD

When choosing a DMARD, there are a variety of factors to consider.

First, the autoimmune / inflammatory state and its severity. These factors also influence what dosage regiment may be adopted, and what monitoring program the patient can expect to undertake.

Second, patient preference. Patients may have responded favourably to some DMARD in the past. Side effect profiles must be considered, too. Patients should understand the likely side effects of each drug and how it may impact their day-to-day life.

Third, likely clinical benefits. The ratio of clinical benefit versus adverse effect profile must be considered. Patients should be informed of expected results and the capacity to which the drug can realistically improve their lives.

Fourth, elimination of risk factors. Patients may be tested for past exposure to specific infections. These blood tests are a necessary component that may rule out what DMARD may be prescribed to the patient. Other patient risk factors must also be considered.

Fifth, patient response. One DMARD may prove effective, whilst another proves to be somewhat ineffective or whose side effects have become too problematic. In some cases, more than one DMARD is required. Often, it comes down to trial and error to determine the optimum DMARD(s) to treat the specific needs of the patient.

Pharmacology of DMARDs

Below, we’ve put together a table of some of the most commonly used DMARDs. How they work – their mechanism of action – has also been added.

DMARD Mechanism of Action
Methotrexate Purine metabolism inhibitor
Hydroxychloroquine Induces apoptosis of inflammatory cells; decreases chemotaxis; targets TNF-alpha
Leflunomide Pyrimidine synthesis inhibitor via inhibition of the enzyme dihydroorotate dehydrogenase
Cyclosporine Calcineurin inhibitor
Chloroquine Suppression of IL-1; apoptosis of inflammatory cells
Azathioprine Purine synthesis inhibitor
Infliximab TNF inhibitor
Anakinra Antagonist of IL-1
Adalimumab TNF inhibitor
Abatacept Binds to CD80 and CD86, preventing T-cell activation
Golimumab TNF inhibitor
Rituximab Acts against CD20 protein on B-cell surface, triggering cell death
Sulfasalazine Suppression of IL-1 and TNF-alpha
Tocilizumab IL-6 receptor antagonist
Tofacitinib Inhibitor of the kinases JAK1 and JAK3, which transmit extracellular data to the cell nucleus – influencing DNA transcription
Certolizumab pegol TNF inhibitor

DMARDs are, then, an effective means not only in the treatment of rheumatoid arthritis but also other autoimmune-inflammatory states, too.

For even more facts on DMARDs pharmacology, register with PharmaFactz today. Check back to our pharmacy blog soon for even more great articles on DMARDs and the valuable role they continue to play in the clinical setting.