This is an approach to treatment and management of Rheumatoid arthritis in which we are going to discuss the goal of treatment , the different methods of management (Physiotheray,Drug therapy, biological therapy and surgical treatment) , the recommended drugs are discussed with detailed illustration of their doses , side effects and mode of action .
• .Suppression of inflammation.
• Conservation and restoration of function.
• Reduction of mortality.
2- Splinting • to decrease pain and muscle spasm.
• to prevent deformity.
3- Physiotheray: It can be started when the phase of exacerbation disappears.
(for relieve of pain and stiffness), no disease modifying effect.
• e.g. - Phenylbutazone 100mg/8 hrs
- Diclofenac 50 mg/8 hrs
- Piroxicam 20 mg/8 hrs
- Fenoprufen 60mg/8hr.
- Ketoprufen 100mg/8hr.
- Indomethacin 25-5018 hrs.
- Aspirin 600-900 mg/4hr.
** Side effects
- Antiplatelt effect ---> haemorrhage.
- Nephrotoxicity, bronchospasm.
- Hepatoxicity.
- GIT irritation.
- Salt, water retension.
Mode of action :
antiprostaglandins through inhibiton of cyclooxygenase enzyme.
COX-2 selective NSAID
• Celecoxib (celebrex) 100-200 mg twice daily.
. • Meloxicam (mobic or melocam ) 7 .5 - 15 mg/day .
(2) Glucocorticoids
• Low dose of prednisolone can be given 5-10 mg (average 7.5mg) daily for symptomatic relieve.
• The addition of 7.5 mg prednisolone daily to NSAID with disease modifying antirheumatic drug, may slow the rate of radiological progression over 2 years in patients with early R.A.
• Prophylaxis against osteoporosis is important in patients under long term steroid therapy.
We can use hormone replacement therapy and/or calcium and vitamin D or bisphosphonate.
Side effects of steroids:
- Hypertension - DM
- osteoporosis - Cataract
- Weight gain - Myopathy
- Peptic ulcer
I.M. depot injections (40-120mg) methyl prednisolone help to control severe disease flares, but should be used infrequently.
Intra-articular steroids
We use long acting steroids. .
Indications :
• Used for joints that remain painful despite of general measures.
• It is the treatment of choice in :
- Bursitis.
- Tenosynovitis.
- Carpal tunnal syndrome.
Side effects :
1- Septic arthritis.
2- Arthropathy.
3- Rebound ain.
• These drugs decrease progression of erosive changes and decrease activity of the disease.
These drugs can be used either singly or in combinations.
• These drugs do not have immediate anti-inflammatory or analgesic effects but will improve symptoms and acute phase response and reduce radiographic progression as later effects so, it is better to be used in early cases.
(A) Antimalarial (Hydroxychloroquine)
Mechanism : -- PG and -- phagocytic activity of PNL .
-- phagocytic activity of PNL
Dose : 200 mg / 12 hr
Response : within 3-6 months.
Side effects :
- Retinopathy
- GIT disturbance
Monitoring : Fundus examination every 6 months.
(B) Sulphasalazine
Mechanism : - Anti-inflammatory..
Dose : 1000 mg /12 hr.
Response : within 3-6 rn
Side Effects :
- Rashes, BM depression
- Megloblastic anemia.
Monitoring : Blood picture and transaminases .
(C) Peniciliamine (less commonly used)
Does: 250 mg / day.
Response: within 3 - 6 months.
Side effects:
• Nephrotic syndrome.
• Pancytopenia (B.M depression).
• Skin rash.
Monitoring: Urine analysis, kidney function tests and blood picture.
(D) Gold IM (less commonly used)
It alters the function of macrophages and complement.
Dose: after does of 10 mg (for idiosyncrasy)
Give 50 mg /week.
Response: within 4-6 months, stopped if there is no response after 6 months.
Side effects:
• Skin rash, thrombocytopenia, leucopenia.
• Nephrotic syndrome.
Monitoring: Blood picture, urine analysis and kidney function tests.
(E) Oral Gold (less commonly used)
Dose: 3 mg/12 hr.
Side effects: - Leucopenia. Diarrhea.
Monotoring: Blood picture, urine analysis.
(F) Methotrexate :
dose: 7.5-15 mg/week.
It can be given oral or s.c. injection, oral folic acid should be given.
Response: 1-3 months.
Side effects:
Hepatotoxicity. - Leucopenia, thrombocytopenia, anaemia.
Alopecia, nausea, diarrhea.
Monitoring : blood picture, liver enzymes..
(G) Leflunomide (Avara)
It prevent pyrimidine production in proliferating, lymphocytes, it is effective as methotrexate but is less likely to suppress bone marrow.
Dose: 1OOmg/day for 3 days , Then 20 mg/day
Side effects:
- Alopecia, Diarrhea, Skin rash
- Leucopenia, thrombocytopenia. - Hypertension.
- Disturbed liver biochemistry. e.g increased transaminases.
(H) Azathioprine
Dose: 1-2 mg/kg/d orally
Side effects: BM depression - Nausea - Infection
• Methotrexate is current first choice DMARDs for RA , many Clinicians select methotrexate as a first line therapy.
• Leflunomide (Avara) can be used as alternative if methotrexate can not be tolerated due to side effects.
• Hydroxychloroquine and sulphasalazine can be used in mild cases or if there is contraindication to methotrexate or leflunomide.
• Gold, penicillamin, cyclosporine and azathioprine have less favourable toxicity/efficacy ratio.
• Combination therapy of DMARDs can be used if the use of single drug is not effective.
(4) Biological Therapy
Anticytokine therapy is now being used:
(a) Blockade of IL-1 and IL-6 with receptor antagonists showing rapid anti-inflammatory effects e.g Anakinra (Kineret) 100mg S.C once daily.
(b) Anti TNF monoclonal antibody.
(5) Surgical treatment
• Tendon repair.
• Nerve decompression
• Correction of deformity.
• Synovectomy.
• Arthrodesis
• Joint replacement.
Important links to visit :
- Rheumatoid arthritis definition,causes and pathology
- Investigations and monitoring of Rheumatoid Arthritis
- Diagnostic Criteria of rheumatoid arthritis and DD from rheumatic fever
- Extra-articular manifestations of Rheumatoid arthritis
- Clinical picture of Rheumatoid arthritis , symptoms and signs
The goals of treatment are:
• Relief of symptoms.• .Suppression of inflammation.
• Reduction of mortality.
Methods of treatment
1- Rest in bed : It is valuable in early cases and during exacerbation.2- Splinting • to decrease pain and muscle spasm.
• to prevent deformity.
3- Physiotheray: It can be started when the phase of exacerbation disappears.
Drug therapy of Rheumatoid Arthritis
(1) NSAIDs(for relieve of pain and stiffness), no disease modifying effect.
• e.g. - Phenylbutazone 100mg/8 hrs
- Diclofenac 50 mg/8 hrs
- Piroxicam 20 mg/8 hrs
- Fenoprufen 60mg/8hr.
- Ketoprufen 100mg/8hr.
- Indomethacin 25-5018 hrs.
- Aspirin 600-900 mg/4hr.
** Side effects
- Antiplatelt effect ---> haemorrhage.
- Nephrotoxicity, bronchospasm.
- Hepatoxicity.
- GIT irritation.
- Salt, water retension.
Mode of action :
antiprostaglandins through inhibiton of cyclooxygenase enzyme.
COX-2 selective NSAID
• Celecoxib (celebrex) 100-200 mg twice daily.
. • Meloxicam (mobic or melocam ) 7 .5 - 15 mg/day .
(2) Glucocorticoids
• Low dose of prednisolone can be given 5-10 mg (average 7.5mg) daily for symptomatic relieve.
• The addition of 7.5 mg prednisolone daily to NSAID with disease modifying antirheumatic drug, may slow the rate of radiological progression over 2 years in patients with early R.A.
• Prophylaxis against osteoporosis is important in patients under long term steroid therapy.
We can use hormone replacement therapy and/or calcium and vitamin D or bisphosphonate.
Side effects of steroids:
- Hypertension - DM
- osteoporosis - Cataract
- Weight gain - Myopathy
- Peptic ulcer
I.M. depot injections (40-120mg) methyl prednisolone help to control severe disease flares, but should be used infrequently.
Intra-articular steroids
We use long acting steroids. .
Indications :
• Used for joints that remain painful despite of general measures.
• It is the treatment of choice in :
- Bursitis.
- Tenosynovitis.
- Carpal tunnal syndrome.
Side effects :
1- Septic arthritis.
2- Arthropathy.
3- Rebound ain.
(3) Disease Modifying Anti-Rheumatic Drugs (DMARDs)
• The introduction of DMARDs is central to the modern management of RA.• These drugs decrease progression of erosive changes and decrease activity of the disease.
These drugs can be used either singly or in combinations.
• These drugs do not have immediate anti-inflammatory or analgesic effects but will improve symptoms and acute phase response and reduce radiographic progression as later effects so, it is better to be used in early cases.
(A) Antimalarial (Hydroxychloroquine)
Mechanism : -- PG and -- phagocytic activity of PNL .
-- phagocytic activity of PNL
Dose : 200 mg / 12 hr
Response : within 3-6 months.
Side effects :
- Retinopathy
- GIT disturbance
Monitoring : Fundus examination every 6 months.
(B) Sulphasalazine
Mechanism : - Anti-inflammatory..
Dose : 1000 mg /12 hr.
Response : within 3-6 rn
Side Effects :
- Rashes, BM depression
- Megloblastic anemia.
Monitoring : Blood picture and transaminases .
(C) Peniciliamine (less commonly used)
Does: 250 mg / day.
Response: within 3 - 6 months.
Side effects:
• Nephrotic syndrome.
• Pancytopenia (B.M depression).
• Skin rash.
Monitoring: Urine analysis, kidney function tests and blood picture.
(D) Gold IM (less commonly used)
It alters the function of macrophages and complement.
Dose: after does of 10 mg (for idiosyncrasy)
Give 50 mg /week.
Response: within 4-6 months, stopped if there is no response after 6 months.
Side effects:
• Skin rash, thrombocytopenia, leucopenia.
• Nephrotic syndrome.
Monitoring: Blood picture, urine analysis and kidney function tests.
(E) Oral Gold (less commonly used)
Dose: 3 mg/12 hr.
Side effects: - Leucopenia. Diarrhea.
Monotoring: Blood picture, urine analysis.
(F) Methotrexate :
dose: 7.5-15 mg/week.
It can be given oral or s.c. injection, oral folic acid should be given.
Response: 1-3 months.
Side effects:
Hepatotoxicity. - Leucopenia, thrombocytopenia, anaemia.
Alopecia, nausea, diarrhea.
Monitoring : blood picture, liver enzymes..
(G) Leflunomide (Avara)
It prevent pyrimidine production in proliferating, lymphocytes, it is effective as methotrexate but is less likely to suppress bone marrow.
Dose: 1OOmg/day for 3 days , Then 20 mg/day
Side effects:
- Alopecia, Diarrhea, Skin rash
- Leucopenia, thrombocytopenia. - Hypertension.
- Disturbed liver biochemistry. e.g increased transaminases.
(H) Azathioprine
Dose: 1-2 mg/kg/d orally
Side effects: BM depression - Nausea - Infection
• Methotrexate is current first choice DMARDs for RA , many Clinicians select methotrexate as a first line therapy.
• Leflunomide (Avara) can be used as alternative if methotrexate can not be tolerated due to side effects.
• Hydroxychloroquine and sulphasalazine can be used in mild cases or if there is contraindication to methotrexate or leflunomide.
• Gold, penicillamin, cyclosporine and azathioprine have less favourable toxicity/efficacy ratio.
• Combination therapy of DMARDs can be used if the use of single drug is not effective.
(4) Biological Therapy
Anticytokine therapy is now being used:
(a) Blockade of IL-1 and IL-6 with receptor antagonists showing rapid anti-inflammatory effects e.g Anakinra (Kineret) 100mg S.C once daily.
(b) Anti TNF monoclonal antibody.
(5) Surgical treatment
• Tendon repair.
• Nerve decompression
• Correction of deformity.
• Synovectomy.
• Arthrodesis
• Joint replacement.
Important links to visit :
- Rheumatoid arthritis definition,causes and pathology
- Investigations and monitoring of Rheumatoid Arthritis
- Diagnostic Criteria of rheumatoid arthritis and DD from rheumatic fever
- Extra-articular manifestations of Rheumatoid arthritis
- Clinical picture of Rheumatoid arthritis , symptoms and signs