Rheumatoid Arthritis Treatment

Fifth stage

Medicine
Lec-3
د.فاخر

26/11/2016

RHEUMATOID ARTHRITIS
Treatment
Goal of treatment
reduce inflammation and pain,
preservation of function,
prevention of deformity.

Pharmacological therapy

*simple analgesic drugs
*NSAIDs
*Topical creams
*Opioid analgesics
*Amitriptylin:
'disease-modifying antirheumatic drug' ((DMARD
*Corticosteroids
Local injections
Surgery


General Principles
Undelayed use of DMARDs
The major goal is full remission
Remission is infrequent with a single DMARD
DMARDs combinations can add benefits with little or no increase in adverse effects

The mainstay of treatment in RA comprises the earlyuse of small-molecule disease-modifying antirheumaticdrugs (DMARDs), and corticosteroids for induction of
remission.
There is evidence that early use of DMARDtherapy improves clinical outcome in RA. Partial or nonresponseto DMARD therapy should prompt escalationof the dose or use of an additional DMARD, with progressionto biological drugs if necessary

SIMPLE ANALGESIA

Paracetamol (1 g 6-8-hourly) is the oral analgesic of choice because of its efficacy, lack of contraindications or drug interactions, long-term safety, low cost and availability. Paracetamol inhibits prostaglandin synthesis centrally in the brain but has little effect on peripheral production of prostaglandins

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

These are among the top five most prescribed drugs in many countries. Oral NSAIDs are often effective for the pain and stiffness of inflammatory disease. Long-acting NSAIDs given at night are particularly helpful for marked inflammatory early morning stiffness. NSAIDs may also reduce bone pain due to secondary malignant lesions.






The major drawback of NSAIDs is gastrointestinal toxicity. Prostaglandins of the E series play a major role in gastroduodenal defence mechanisms. By depleting mucosal prostaglandin levels, aspirin and NSAIDs impair this 'cytoprotection', resulting in mucosal injury, erosions and ulceration. NSAIDs are an important aetiological factor in up to 30% of gastric ulcers.
IMPACT OF NSAID-INDUCED GASTRIC BLEEDING
Endoscopic evidence of peptic ulceration is found in 20% of NSAID users even in the absence of symptoms
1% of patients with RA or OA are hospitalised each year with gastrointestinal bleeding
Annual mortality in people in the US and in the UK higher than deaths from diseases such as myeloma, asthma, cervical cancer or Hodgkin lymphoma

RISK FACTORS FOR NSAID-INDUCED ULCERS

*Age > 60 years
*Past history of peptic ulcer
*Past history of adverse event with NSAIDs
*Concomitant corticosteroid use
*High-dose or multiple NSAIDs
*Individual NSAID-highest with piroxicam, ketoprofen; lower with ibuprofen

PRINCIPAL INDICATIONS FOR ORAL OR PARENTERAL CORTICOSTEROID

1-For rapid, short-term (1-3 months) control of marked synovitis or systemic inflammation while awaiting efficacy from slow-acting antirheumatic agent
2-For life-threatening (e.g. vasculitis) or organ-threatening (e.g. kidney, lung, eye) inflammatory multisystem disease
3-For primary treatment of polymyalgia rheumatica
4-For control of inflammatory disease during pregnancy


CORTICOSTEROIDS IN RHEUMATOID ARTHRITIS
Systemic corticosteroids have disease-modifying activity, but their primary role is in the induction of remission in patients with early RA who are starting synthetic DMARD treatment.
Various regimens have been usedbut there is little evidence to suggest that one is superior to another.
One strategy is to give a high dose oforal prednisolone initially (60 mg daily) and to reduce and stop this gradually over a period of 3 months as theDMARD starts to take effect.

LOCAL INJECTIONS

Intra-articular corticosteroids are primarily indicated when there are one or two ‘problem joints’ with persistent synovitis despite good general control of the disease. Although corticosteroids are very useful, they alsohave significant adverse effects (p. 776). In the contextof RA, osteoporosis is probably the most importantsince this is a known complication of RA, even in the absence of corticosteroid therapy. Accordingly DEXA
scanning followed by bone protection should be considered in any patient with RA who is expected to be on more than 7.5 mg prednisolone daily for more than 3 months

Disease-modifying antirheumatic drug "DMARDs"

Classification of DMARDs
1-Non-Immunosuppressive agents (“joint effective agents”)
2-immunosuppressive agents (“joint & systemic effective”)
3-Biological agents

1-Non-Immunosuppressive agents (“joint effective agents”)

Sulfasalazine
Hydroxychloroquine
Gold salts (e.g. sodium aurothiomalate)
D- penicillamine


2-immunosuppressive agents (“joint & systemic effective
Methotrexate
Azathioprine
Leflunomide
Ciclosporine
Other cytotoxic drugs

Methotrexate

Methotrexate is the anchor DMARD in RA. It is usually given as a starting weekly oral dose of 7.5–10 mg and this is increased in 2.5 mg increments every 2–4 weeks until benefit occurs or toxicity is limiting. The maximum recommended dose is 25 mg. The benefits of methotrexate usually start to appear within 1–2 months but a 6-month course should be given before concluding that it has been ineffective.

The most common adverse effects

are nausea, vomiting and malaise within 24–48 hours ofadministration.
Patients who experience these can sometimes be successfully treated with subcutaneous methotrexate.
Folic acid (5 mg/week) reduces the incidence of adverse effects without reducing efficacy.

Cyclophosphamide, azathioprine, and cyclosporine

are immunosuppressive drugs that are effective agents in treating RA. In addition to the risk of both common and unusual infections, cyclophosphamide carries a risk of bladder and late lymphoid malignant disease; the latter risk may also be present with azathioprine.



Among the oldest of are gold salts. Given as weekly injections, gold thiomalate or thioglucose is effective in controlling disease in many patients; a few patients go into true and complete remission. However, many patients experience side effects, including bone marrow suppression, glomerulonephritis, and rash.


3- Biological Treatment (Anticytokines)
These drugs are more effective than standard DMARDs (with a faster onset of action, greater clinical efficacy and sustained benefit) but because of their cost many countries have set restrictive guidelines for their use.
Current UK recommendations are that they should be initiated only in active RA when an adequate trial of at least two other DMARDs (including methotrexate) has failed.

1- Anti-TNF therapy (Infliximab)

is the first-line biological drug in RA.
Several agents are available.
With the exception of infliximab, which must be prescribed with methotrexate to reduce the risk of neutralizing antibodies developing, these agents can be used as monotherapy. In clinical practice, however, most are co-prescribed with methotrexate, as this is more efficacious.
The main adverse effects are serious infections and reactivation of latent tuberculosis
2- Competitively blocks binding of IL-1 to its receptor (Anakinra)
3- Monoclonal antibody that binds CD20 antigen on B-cells surface (Rituximab)

EXAMPLES OF COMMON USEFUL SURGICAL PROCEDURES FOR MSK DISORDERS

Soft tissue release decompression
Carpal tunnel(Median nerve) compression
Synovectomy
Joint replacement arthroplasty
Arthroplasty