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)

Methotrexate 

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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Most effective ways to strengthen your bone

Osteoporosis is one of the most disabling problem in elderly, especially in females. In osteoporosis there is weakness of bone strength. Inorder to escape from osteoporosis you should take care of your bones from childhood itself. 

Following tips will help you to strengthen your bone.

1. Growing phase of bone is up to 21 years, you should consume foods with maximum calcium content this phase. Here are some foods that are rich in calcium.

(a) Milk and milk products.

(b) Green leafy vegetables.

(c) Foods with high vitamin C will help in calcium absorption.

(d) Orange.

(e) Gooseberry.

2. Consumption of foods that's rich in calcium is better than consuming calcium supplements, take calcium supplements if prescribed by doctor and ensure balanced diet.

3. For strong and healthy bones regular physical exercise is essential. Walking and swimming are best for bone strengthening.

4. Give more attention in bone strengthening from 30 years onward.

5. In females postmenopausal osteoporosis is common, estrogen replacement help to reduce it. Hormone replacement therapy contains phytoestrogen, which functions as estrogen in the body.

6. Reduce the salt intake, excessive salt causes weakening of bone strength.

7. Avoid excess sugar, carbonated drinks and coffee. The phosphoric acid in them cause loss of calcium through urine.

8. Avoid physical activities that create over burden to bones after 45 years.

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Association of age and sex with osteoarthritis

Age and osteoarthritis : Osteoarthritis is a common problem in the community. It has several important risk factors of which one of the most important risk factor is age. Association between age and osteoarthritis is as below.

1. Osteoarthritis is less prevalent in people below 45 years. Type of osteoarthritis seen in this group usually affect single joint. The most common cause  of this is trauma and injury.

2. As the age advances the chance of getting osteoarthritis also increases this is seen up to 65 years .

3. In elderly more joints are involved compared to young people who predominantly show affection of single joint.

4. Radiological evidence of osteoarthritis is seen  in people under 40 years even if they do not have symptom.

5. In people aged over 70 years more than 50 percentage will have osteoarthritis of hand.

6. Joint are protected from osteoarthritis by several mechanism, these protectors fails with age.

7. One of the important protective mechanism is cartilage in the joint, as age advances there is thinning of cartilage in the joint. So the joint experience increased stress with load.

8. Muscle that bridge the joint protect the joint from increasing stress, as age advances there is weakening of the muscle strength.

9. As a part of  ageing ligaments stretch, so they cannot absorb the stress.

Sex difference in osteoarthritis

1. In mild osteoarthritis there is no gender difference

2. Female predilection is seen in severe grades of osteoarthritis

3. Severe disease is seen in older age groups in knee and hand osteoarthritis.

4. Older women are at increased risk for osteoarthritis of all joints ,it is seen in sixth decade,this is due to loss of female sex hormone after menopause.

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Need of patient education about osteoarthritis.

Helping the patient to understand about osteoarthritis is important. It is a progressive wear and tear disease of old age. Poor understanding of the disease will lead to negative attitude in patients. For example ignorance about the disease may lead to lack of activity which further aggravate the disease. Patient education is an essential component of  treatment due to the following reasons.

Psychological and social factors will alter the effect of disease, proper education of the patient regarding the disease and effect will reduce the pain, distress, disability and it will improve the treatment compliance.

To protect the affected joint from excessive loading

1. Reduce the weight.

2. Patient should consume low fat, carbohydrate rich low calorie food for weight reduction.

3. Avoid inappropriate daily and occupational activities example knee lifts.

4. Use walking sticks.

5. Wear shock absorbing footwear.

6. Correct the disparity in leg length with shoe rise.

7. Tubular loose knee support may reduce the pain.

8. Use wedge insoles.

9. Proper advice should be given to maintain the normal joint function.

10.Advice aerobic fitness such as walking and swimming to maintain the joint motion and stability.

11. Do muscle strengthening exercise.

12. Regular physical activity.

13. Avoid over activity on good days because that may increase the pain and reduction of activities on subsequent days.

Proper modification of work place and home activities are required.

Advice regarding sexual activities should be given to the patient and the partner with hip osteoarthritis.

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Beneficial effect of exercise in osteoporosis

Osteoporosis is characterized by low bone strength. This condition is more common in females after cessation of periods (postmenopausal). The disease is associated with increased risk of fracture in various sites of body.

The main aim of treatment is strengthening of bone and muscles, prevent fall and fracture. The beneficial effects of exercise in osteoporosis patients are discussed below.

Exercise in young individuals help to attain maximum bone mass and strength.In elderly weight bearing exercise help to prevent the bone loss, but it wont increase the bone mass. The benefits decreases if they stop excise. There will be better effects if the exercise is done for longer period. Exercise should be done at least 3 times a month.

Exercise also help to improve the following

The strength of nerves and muscles.

Improve the coordination.

Improve the balance 

Thus help to reduce the fall.

Various exercise programs for osteoporosis
Selection of exercise program depends on the  physical condition and preference of the patient.

1. Walking program

5. Use of gym equipment.

2. Dancing

3. Racquet sports.

4. Cross country skiing

If the patient cannot do the above mentioned ones swimming and water sports are advised, but this has low effect on bone. This will help to strengthen the muscles.

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Treatment of Osteoarthritis

Goals of osteoarthritis treatment are the following

1. Control of pain.

2. Functional improvement.

3. Decrease the handicape due to osteoarthritis.

4. Improve the quality of life.

5. Educate the patient about the disease.

6. Decrease the drug related side effects.

Number of modalities are available to achieve these goals. The main problem of the patient is pain and physical handicap due to osteoarthritis. Cause and treatment of it require special attention.

Given below are the treatment modalities 

1. Counselling.

2. Patient education.

3. Physical therapy.

4. Occupational therapy.

5. Drugs.

6. Complementary medicine.

7. Surgery.

Reduction of pain  and stiffness of joint with following drugs

1. Analgesics.

2. Intermittent/regular analgesics (acetaminophen).

3. Topical NSAIDs.

4. Topical capsaicin.

5. Oral NSAIDs.

6. Oral glucosamine sulfate.

7. Peri- and intra-articular corticosteroid injection.

8. Hyaluronic acid injection.

9. TENS and nerve blocks for severe pain.

Reduction of the impact of pain and disability

Due to the pain and disability of osteoarthritis patients experience depression, anxiety, fibromyalgia. Treatment of these aspects is also advised

Modification of  patient environment to reduce handicap

Surgery is reserved for those patients with severe pain and disability.

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What are the risk factors for osteoarthritis

Osteoarthritis is very common in the community and there are certain factors that place the patient at high risk for osteoarthritis. These factors act in two ways

1. They may increase the joint susceptibility to development of  osteoarthritis.

2. They increase the load on the joint

3. Combination of above mechanism

Following are the risk factors for osteoarthritis.

1. Age is the most potent risk factor for osteoarthritis,as age advances the risk also increases.

2. Gender, females are at increased risk for osteoarthritis. The role of sex hormone is indicated by increased risk after menopause.

3. Heritability, osteoarthritis is a heritable disease. Heretability varies depending on the joint. This is high in hip osteoarthritis.

4. Local factors in the joint. This will lead to uneven distribution of weight and increased focal stress example malalignment across the joint, increased mobility of joints, congenital joint abnormality.

5. Obesity increases the load across the joint.

6. Repeated use of joints and injury will cause osteoarthritis especially in sportsmen.

7. Fracture and trauma increases the risk.

8. Cigarette smoking.

9. Occupation - Certain occupation is at risk for this condition. 

   (a) Miners - osteoarthritis of hip, knee, shoulder.

   (b) Cotton workers - hand osteoarthritis.

   (c) Farmer - hip osteoarthritis

10. Osteo arthritis can  also develop secondary to certain disease.

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Why obesity lead to osteoarthritis ?

Obesity or overweight is a common problem in community. It will lead to a variety of health problem. One of the important health problem in obese individual is osteoarthritis. Three to six times body weight is transmitted across the knee during single-leg stance. Any increase in weight may be multiplied by this factor to reveal the excess force across the knee in overweight persons during walking. Obesity’s effect on the development and progression of disease is mediated mostly through the increased loading in weight-bearing joints that occurs in overweight persons. 

1. Obesity is closely associated with knee osteoarthritis,  in those who have body weight more than 50 per cent above their ideal body weight when compared to those people with ideal body weight. The risk is more in women than men Risk ratio is of  9.0 for women and  4.5 for men.

2. One of the interesting factor noticed is that obesity does not seem to be  a strong risk factor for  hip osteoarthritis, compared to knee osteoarthritis.

3. At the knee joint, obesity is a predisposing factor for development of disease than it follows knee osteoarthritis.

4. In some people osteoarthritis at knee may or may not be associated with symptoms, but it produce radiographic change.

5. Once the obese people develop knee osteoarthritis the painful knee also lead to sedentary lifestyle. The same thing happens with obesity.

6. For a given damage to knee joint obesity increases the pain. Obesity also increases the severity of disease.

7. Malalignment (varus/valgus knee alignment) increases the risk for osteoarthritis.

There are  two types of limb malalignment in knee joint in the frontal plane,
  1.Varus deformity in which the stress is placed across the medial compartment of the knee joint.
  2.Valgus deformity which places excess stress across the lateral compartment of the knee.

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Exercise in knee joint osteoarthritis

Osteoarthritis pain occur during activity in weight bearing joints such as hip and knee. This will lead to physical inactivity. As osteoarthritis is very common this will lead to significant public health concern. Physical inactivity lead to increased risk for heart disease and for obesity.Exercise capacity is poor in  those with osteoarthritis of knee joint.

There is weakness of muscles over the knee joint in osteoarthritis. Since adequate muscle power is needed for joint protection muscle weakness results in further damage to the joint and decreases the exercise capability. Degree of weakness correlate with severity of joint disease and degree of limitation of mobility of joint.

Causes of muscle weakness

1.Decrease strength with age

2.As pain occur during activity ,there is tendency for physical inactivity this will lead to disuse atrophy

3.Alteration in gait as a protective mechanism decreases the load on affected joint and further decreases the muscle power.

Exercise program in osteoarthritis

For knee and hip joint osteoarthritis exercise improves the power and reduces the pain.

Effective exercise program are

1.Aerobic exercise 

2.Resistance training

Resistance training is aimed at strengthening of muscle power. Exercise is maximum effective if the affected people are trained for their daily activities. Certain exercise increases the pain in joints they should be avoided. Strengthening of muscle by repeated bending of knee against resistance. It is done by flexing and extending the knee joint. Low impact exercise such as water aerobics and water resistance training is also found to be useful. This is better tolerated than loading exercise such as running. For getting maximum benefit from exercise patient should be referred to an exercise class or to a therapist to plan individual home based exercise regimen.

Major challenge in exercise program is lack of compliance. Trial showed 30 to 50 percentage of people stopped exercise after 6 months and less than 50 percentage continued after one year. Previous history of successful exercise is the strongest predictor for continued exercise in a given patient.

Role of physician

1.At each visit he should reinforce the exercise prescription.

2.Help the patient to identify obstacles in continuing exercise.

3.Identify convenient time for exercise daily.

It is also observed that calorie restriction along with exercise is very effective in decreasing pain. It is shown that early exercise and muscle strengthening help to improve the cartilage function on joint by MRI study.

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Clinical features of osteoarthritis

Most common manifestation of osteoarthritis is joint pain and it is activity related pain occur during activity or immediately after the use of joint and it decreases gradually.

Site of pain - example

1. Hip and knee pain going up and down stairs.
2. Pain in weight bearing joints  while walking.
3. Hand osteoarthritis - pain while cooking.

Nature of pain.

Early in the disease, pain is present only when the affected joint is overused, but later the pain become constant and present even at night. This is associated with stiffness of joint. If early morning stiffness is present, it is very brief usually less than 30 minutes.

Osteoarthritis of knee joint.

In osteoarthritis of knee joint, pain occur on bending the knee. Some people experience buckling, catching and locking of the knee joint. Osteoarthritis of knee joint is the most common cause of chronic knee pain in persons over 45 yrs. In hip osteoarthritis restriction of hip movements will occur.

Investigation in osteoarthritis.

No blood test is required for evaluation of patients with osteoarthritis.

Tests that may be done.

1. Synovial fluid analysis.
2. Xray of joint.
3. MRI test.

Synovial fluid analysis.
If the WBC count more than 1000 it indicate inflammatory arthritis or gout

Xray

Correlate poorly with disease activity and joint pain .It may be normal in the early disease.It is indicated if the joint pain does not respond to usual management.

White arrow indicates joint space reduction compared to opposite side

MRI

Not a routine part of osteoarthritis evaluation.

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