9 May 2015

What is the role of conventional DMARD in rheumatoid arthritis treatment

DMARD are disease modifying antirheumatic drugs, they are so called because of their ability to prevent and slow the structural damage to joint and save the joint in rheumatoid arthritis.These are known as slow-acting "second-line drugs.Prior to the invention of these drugs treatment is aimed to reduce the pain and discomfort to people than slow the actual underlying disease process.DMARD have thus revolutionized the treatment and elevated treatment goal. 

What are the advantages of DMARDS in RA?
1.These agents substantially reduce the inflammation in joints.
2.Prevent or slow down the joint damage.
3.Help to preserve the joint structure and function so the affected person can lead normal life and enable to do all daily activities as far as possible.

When to start DMARD?
Since the critical period in RA is first year of onset of disease, bone and joint damage occurs early, DMARDS cannot reverse the existing damage already occurred, they can only protect the joint from further progression of disease process.It is better to start them early to avoid joint destruction.As soon as the person is diagnosed with this disease Rheumatologists now start with a DMARD.Methotrexate is the most commonly prescribed drug.The faster the patient is strated on DMARD sooner it slow down the joint damage.

How they act in RA?
They will act on specific part of immune system and bring down the abnormally increased immune response.Basic pathology in RA is abnormal immune response which damage the joints.Earlier treatment with them have improved the function and reduced the structural damage to joint that is even within months of diagnosis.Most people need aggressive secondline drugs to treat the situation that is methotrexate.

How long it take to get improvement in disease?
The time requied to produce improvement varry depending on individual agent.
4 to 6 weeks of treatment with methotrexate
1 to 2months with salfasalazine
2 to 3 months for hydroxychloroquine
Sometime they need to take for years at varying doses to get optimal results

Conventional DMARDS  in Rheumatoid arthritis treatment 
DMARDS come in variety of forms and are listed below. 
Methotrexate (Trexall, Rheumatrex, Otrexup),leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine)

This is the initial DMARD of choice and is the main drug for combination therapy.This is an immune suppressing agent and decreases the joint inflammation.Since 1986 it is approved for treatment of RA.This is the initial second-line drug because of the following. 
1.Methotrexate is effective and it has infrequent side effects compared to other DMARDS.
2.Dose adjustment of methotrexate is flexible.Dose adjustment done as per need.
Side effects of this drug are ,it may affect bonemarrow and liver  rarely cause cirrhosis of liver and allergic reaction in lung.So regular monitoring of liverfunction and complete blood count is required in all people  while on this drug.Taking folic acid recommended to  reduce the risk of methotrexate side effects.
Dose of methotrexate is 10–25 mg/week orally or SQ Folic acid 1 mg/d to reduce toxicities.Other common side effects are mouth ulcers fatigue, hair loss ,vomiting and loose stool.Before starting treatment check CBC, LFTs Viral hepatitis panel and Chest x-ray.
Monitor CBC, creatinine, LFTs every 2–3 months while on treatment.

Leflunomide (Arava) 
Helps to relieve the symptoms and slowdown the progression of the RA.Clinical efficasy similar to methotrexate.Common side effects of this dugs are hair loss, diarrhea, rash in some people.Serious side effects include increased susceptibility to infection,liver damage, bone marrow suppression.This drug is not safe in pregnancy.As it produces birth defects it should not be taken during pregnancy and those women who want to become pregnant while on drugs.Dose is 10–20 mg/d.Before starting therapy blood count,liver function test and viral hepatitis panel should be done. While on this agent regular monitoring of CBC, creatinine, LFT every 2–3 months is recommended.

Hydroxychloroquine  (Plaquenil) 
It has been used for long periods  to treat RA..But it wont produce radiographic improvement.Dosage of this drug is 200–400 mg/d orally(=6.5 mg/kg)
This is used  in early mild cases and in combination therapy with other DMARD. The common side effect of this drug include upset of stomach, diarrhea,vomiting ,headache. muscle weakness ,skin rashes, and vision changes.Prior to starting this drug eye examination is done in all people who are more than 40 years old and those with past history of eye disease.People on this drug require regular monitoring of vision by an eye doctor (ophthalmologist) every year after starting drug.Other serious adverse reactions of this drugs are toxicity of heart and abnormality in blood count.

Sulfasalazine (Azulfidine)
This is an oral drug used to treat RA along with other antiinflammatory agents.This drug is usually well tolerated by people.The common side effects are stomach upset rash,vomiting and diarrhea.The serious side effect is low blood count thus predispose to infection.As Azulfidine  contain  sulfa and salicylate compounds this should  be avoided in people with past history of allergy to sulfa.Initial dose of drug is 500 mg orally twice daily and maintenance dose is 1000–1500 mg twice daily.Before starting these drugs blood count,liver function test and G6PD level need to be tested.For people on salfasalazine blood count should be monitored every 2–4 weeks for first 3months,then every3 months

Conventional  agents may be used alone or in combination in the treatment of RA 

Immunosuppressants in the treatment of RA
Immunosuppressants are used in the treatment of refractory aggressive case of RA , where all other therapy fails.Also in those people with severe complication of RA that is blood vessel inflammation.They include azathioprine (Imuran), cyclophosphamide(Cytoxan), cyclosporine and chlorambucil(Leukeran), 
These agents may suppress the bonemarrow and produce anemia,low platelet count and low toatal WBC  count.Thus increases the risk for infection,and bleeding.
Agents like Gold ,Pencillamine are rarely used nowadays due to poor clinical efficacy and toxic profile. 

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