Disease Modifying Anti Rheumatic Drugs (DMARD)
by DR ARVIND CHOPRA
An Era of New Therapy using Biologic DMARD and Synthetic Target in Treating Rheumatic Diseases:
SUMMARY POINTS/ FACT SHEET
Disclaimer: These are clinical practice guidelines and general information for patients. It is mandatory to consult rheumatologist prior to therapeutic use. Do not self-treat in any case.
Introduction: In this article, some basic descriptions are provided to understand the disease modifying anti rheumatic drugs (DMARD) which are pivotal in the management of several autoimmune immune inflammatory rheumatic disorders. Rheumatoid arthritis (RA) is a typical example and the focus in this fact sheet. Conventional DMARDs include Hydroxychloroquine, Sulfasalazine, Methotrexate, Leflunomide and are often used when patients are first diagnosed with RA. Methotrexate is the most popular and pivotal DMARD in RA. Conventional DMARD have been used to treat several rheumatological disorders for over 40 years and can be used for prolonged periods lasting several years. Biologic drugs are advanced DMARD in the form of injections and used when disease is aggressive and not well controlled with conventional DMARD. In RA, methotrexate is usually continued along with a Biological DMARD for better long-term response... There is a wide variety of Biologic DMARD agents belonging to different classes (such as anti-tumour necrosis agents, B-cell inhibitors, Interleukin 6 inhibitors) with almost equal efficacy and safety and the choice is often based on preference by the patient, experience of the specialist, price of the drug and ease of administration and monitoring. In the last decade a new class of very effective DMARD drugs called JAK inhibitors has been approved to treat RA and other disorders. JAK inhibitors are oral drugs with very specific action on a particular inflammatory process in RA and other disorders and are now being considered at par with Biological DMARD agents. It should be noted that no DMARD will work in every patient. This is also true of Biologic agents and JAK inhibitors. But based on the clinical profile of RA and presence of complications and other coexisting diseases, a rheumatologist can make a good decision on the choice of DMARD. Sometimes, these drugs need to be changed when the disease control is inadequate or in case of drug side effects or some complication
All types of DMARDs require selection and monitoring by rheumatologist.
- DMARDs are special drugs that act on the immune system to reduce the signs and symptoms and bone damage and other systemic complications of autoimmune inflammatory arthritis disorders like rheumatoid arthritis and ankylosing spondylitis
- DMARDs are not symptomatic drugs like pain killers (Crocin TM), steroids (wysolone TM) and anti-inflammatory drugs (like Voveran TM and Naprosyn TM)
- DMARDs are slow acting and may take several weeks to months to show optimum effect. The clinical effect of hydroxychloroquine may be obvious after 12 weeks and that of methotrexate after 6 weeks.
- Over time, long term use of DMARDs leads to good control of disease with reduction in requirement of pain killers, steroids and anti-inflammatory drugs.
- DMARDs are prescribed by specialists like rheumatologists
- DMARDs need careful supervision and repeated monitoring to check for efficacy and prevent and avoid drug related side effects and toxicity.
- DMARDS are potent drugs and can produce several side effects if not supervised properly- susceptibility to infections, anemia, low blood cell counts, abnormal liver function and hepatitis, abnormal kidney functions and kidney failure, skin lesions, poor digestion and acid related symptoms.
- When on DMARD regular laboratory monitoring is required- blood hemoglobin and white cells and platelet count, liver and kidney functions, routine urine testing.
- When monitored regularly, DMARDs are relatively safe and its side effects can be prevented or controlled early and treated properly
- Traditional DMARD include methotrexate, hydroxychloroquin, sulf asalazine and leflunomide.
- In recent times, biological DMARDs with very specific and potent therapeutic effect on some important component of the immune system have been introduced to treat several types of severe and bad arthritis which have several complications including deformed joints.
- Biologic DMARD are very effective in the management of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and several other inflammatory arthritis and can produce complete control/remission in several patients
- Biologic agents target specific components (such as cytokines, cells, and receptors) of the body's immune system that are responsible for the severity and complications.
- Biologic DMARDs control pain and other symptoms rapidly and the effect can be very dramatic.
- The decision to start biologic DMARD is taken with utmost care by the rheumatologist
- Biologic agents are expensive drugs
- Biologic agents are begun after detail evaluation of several clinical, investigation and socioeconomic factors
- RA and similar inflammatory arthritis are lifelong disorders and need long term medication
- and therefore, the rheumatologist will carefully decide how long to take biologic DMARD as per an individual case.
- Biologic DMARD can be used for a short course to quickly control the disease flare and severity but this needs expert handling by the rheumatologist.
- Single or few injections for just symptomatic relief are not recommended
- Patients on biologic DMARD may also require several other medicines (such as analgesics, anti-inflammatory (NSAIDs), immunosuppressive, conventional DMARD, ironcalcium supplements etc) but the need becomes lesser in time as arthritis improves
- All patients on Biologic DMARD are closely monitored to ensure improvement and detect any early drug toxicity; repeated laboratory blood tests are required
- Biologic DMARD are not pain killers but through superior disease control often reduce the requirement of analgesics and steroids; the requirement may become nil
- Biologic DMARDs increase the risk for infections including tuberculosis.
- Prior to beginning, all patients are carefully screened for tuberculosis and hepatitis
- Compared to routine DMARD and steroids, biologic DMARDs are much more safer; side effects connected with gut, liver, lungs and heart are uncommon
- Biologic DMARD, especially if begun early, effectively prevent or at least reduce the chances of several bad complications of rheumatoid arthritis and other inflammatory arthritis such as joint deformities, osteoporosis, and ischemic cardiac and blood circulation disorders
- Only rheumatologists are authorized to prescribe and use biologic DMARD
- Biologic DMARD are expensive drugs but there are several schemes announced by the manufacturers from time to time to enable some patients to afford them
- In recent times, several companies in India are engaged in research and development of BIOSIMILAR DMARDs. Though differing in precise formula, Biosimilar drugs are considered equivalent to original Biological drugs in efficacy and safety and also approved after stringent evaluation by drug regulatory authorities. Biosimilars of ln fliximab, etanercept, adalimumab and rituximab are now available in India are likely to cost less than original Biologic drugs.
SYNTHETIC TARGET DMARD (JAK Inhibitors):
- Another new category of DMARDs have emerged called synthetic targeted. They are
- considered to be as effective as 'biologic agents' and act within the cell on critical pathways that transmit signal from cell surface to nucleus.
- Two new synthetic target dugs in the Indian market are Tofacitiniband Baricitinib. They inhibit a complex signal mechanism in cell called Janus Kinase (JAK) and therefore are called JAK inhibitors. They are approved for use in rheumatoid arthritis.
- JAK inhibitors can be combined with oral methotrexate in severe and difficult to treat RA and other disorders like psoriatic arthritis.
- JAK inhibitors rapidly control pain and other symptoms in RA.
- JAK inhibitors are oral drugs (tablets) and are expensive. However, Tofacitinib is now being manufactured and marketed in India under several trade names with a much lesser cost.
- Prior to beginning, patients need to carefully screened for infections, blood or any systemic disorders.
- The side effect profile of JAK inhibitors is similar that of other DMARD but careful monitoring for infections (especially herpes zoster) and of lymphocytes, kidney functions and blood lipid/cholesterol is required.
- Patients on JAK inhibitors need to be carefully monitored similar to conventional and biologic DMARD
- These drugs can only be prescribed by rheumatologist and need careful supervision.