Behandlung von rheumatoider Arthritis

Was ist rheumatoide Arthritis?

Rheumatoid arthritis (RA) is a chronic systemic disease. Early diagnosis of RA and effective treatment with disease-modifying antirheumatic drugs (DMARDs) are essential to reduce joint destruction and disability. An increasing range of DMARDs is now available.

Late diagnosis of RA greatly increases the risk of erosive joint damage. Once mechanical damage has occurred, pain and joint deformity often require aids and appliances and, eventually, surgery. Current guidance is that patients with suspected RA should be referred to a rheumatologist as soon as possible so that disease-modifying agents can be started early in the condition.¹

The window of opportunity in which disease-modifying drugs can prevent joint damage is only a few months.²

• The National Institute for Health and Care Excellence (NICE) recommends referral of any person with suspected persistent synovitis of undetermined cause for specialist opinion. Refer urgently if any of the following apply:³

  • Die kleinen Gelenke der Hände oder Füße sind betroffen.

  • Mehr als ein Gelenk ist betroffen.

  • Zwischen dem Auftreten der Symptome und dem Aufsuchen eines Arztes liegen drei Monate oder mehr.

• Do not avoid referring urgently any person with suspected persistent synovitis of undetermined cause whose blood tests show a normal C-reactive protein (CRP) and ESR or a negative rheumatoid factor.

Behandlung von rheumatoider Arthritis

• Whilst waiting for specialist assessment, non-drug measures and symptomatic treatment - such as simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) - can be instituted. At any stage the use of simple analgesia should be considered as an adjunct. Drugs to suppress neuropathic pain, such as carbamazepine or amitriptyline, may also be beneficial.

• Management should include a multidisciplinary team (MDT). All patients should have access to a range of professionals, including GP, rheumatologist, nurse specialist, physiotherapist, occupational therapist, dietician, podiatrist, pharmacist and social worker.

Monitoring disease³

• In people with recent-onset active RA, measure CRP and key components of disease activity (using a composite score such as DAS28) monthly until treatment has controlled the disease to a level previously agreed with the person with RA.

• The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the number of tender and swollen joints (out of a total of 28 - shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees), the ESR, and the patient's 'assessment of global health'. A DAS28 score greater than 5.1 implies active disease, less than 3.2 - well-controlled disease, and less than 2.6 - remission.⁴

• Screen for comorbid conditions - eg, osteoporosis, depression, infection and cardiovascular disease (CVD).

Non-drug management

The importance of the MDT is emphasised in the NICE guidance:³

• RA patients should have access to a named member of the MDT who is responsible for co-ordinating their care (often a specialist nurse).

• RA patients should have easy access to physiotherapy, occupational therapy, psychological services and podiatry. There should be regular review, particularly with physiotherapy and occupational therapy.

• The core members of the MDT will be the GP, the rheumatologist, physiotherapists and occupational therapists. Other specialties that may need to be involved include podiatrists, orthotists, dieticians, pharmacists and neurologists.

• Exercise has been found to reduce bone loss in premenopausal women with RA.

• Pain clinic specialists may be able to advise on non-drug management options, such as transcutaneous electrical nerve stimulation (TENS) and behavioural approaches.

• Non-clinical issues may need the assistance of social workers, voluntary organisations and wheelchair services.

NSAIDs

Traditional NSAIDs include ibuprofen, diclofenac and naproxen. COX-2 drugs include celecoxib and etoricoxib.

NICE recommends:³

Considering an oral non-steroidal anti-inflammatory drug (traditional NSAID or COX-2 selective inhibitor) when control of pain or stiffness is inadequate. Take account of potential gastrointestinal, liver and cardiorenal toxicity, and the person's risk factors, including age and pregnancy. When treating symptoms of RA with oral NSAIDs:

• Offer the lowest effective dose for the shortest possible time.

• Offer a proton pump inhibitor (PPI); and

• Review risk factors for adverse events regularly.

NSAIDs improve symptoms and signs of RA. They are highly effective and many RA patients rely on them, but they do not slow progression or long-term disability.

In patients already taking low-dose aspirin, paracetamol or a compound analgesic should be considered before giving an NSAID. NSAIDs should be used at the lowest effective dose and, if possible, withdrawn when a good response to DMARDs is achieved.⁵

COX-2 selective drugs have very similar efficacy to standard NSAIDs, although patients report individual differences. COX-2 selective NSAIDs are more expensive.

COX-2s are contra-indicated in coronary heart disease, cerebrovascular disease, peripheral arterial disease, and mild-to-severe heart failure.⁵

NICE has produced guidance dealing with the management of chronic pain.⁶

Corticosteroids³

• Short-term treatment with glucocorticoids may be used for managing flares in adults with recent-onset or established disease to rapidly decrease inflammation.

• In adults with established RA, long-term treatment with glucocorticoids may be continued when:

  • The long-term complications of glucocorticoid therapy have been fully discussed; and

  • All other treatment options (including biological and targeted synthetic DMARDs) have been offered.

• Short-term bridging treatment with glucocorticoids may be used when starting a new conventional DMARD (cDMARD - see below).

Intra-articular corticosteroid injections can be used to:

• Provide symptomatic relief pending the onset of DMARD effect.

• Alleviate symptoms in particularly troublesome joints where the overall disease control is good.

• Deal with monoarthritis/oligoarthritis in instances when DMARDs are deemed inappropriate.

DMARDs³

See also the separate Disease-modifying antirheumatic drugs (DMARDs) article.

• First-line treatment with cDMARD monotherapy using oral methotrexate, leflunomide or sulfasalazine should be started as soon as possible and ideally within three months of onset of persistent symptoms.

• Hydroxychloroquine can be used for first-line treatment as an alternative to oral methotrexate, leflunomide or sulfasalazine for mild or palindromic disease.

• Additional cDMARDs (oral methotrexate, leflunomide, sulfasalazine or hydroxychloroquine) should be used in combination in a step-up strategy when the treatment target (remission or low disease activity) has not been achieved despite dose escalation.

Biologische Therapien

Biological therapies (cytokine modulators) have been shown to be effective in the treatment of RA, including patients resistant to methotrexate. The following are approved for treatment of RA:⁷

• Tumour necrosis factor (TNF) inhibitors: adalimumab, certolizumab pegol, etanercept, golimumab, infliximab.

• Anti-interleukin-1 therapy: anakinra.

• T-cell co-stimulator modulator: abatacept.

• Anti-CD20 therapy: rituximab.

• Anti-interleukin-6 receptor therapy: tocilizumab.

NICE recommends that in addition to low-dose glucocorticoids, two trials of six months of traditional DMARD monotherapy or combination therapy (at least one including methotrexate) should fail to control symptoms or prevent disease progression before a biological therapy be recommended.

A trial of a DMARD is defined as being normally of six months, with two months at standard dose, unless significant toxicity has limited the dose or duration of treatment.³

TNF Inhibitors

• Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept, all in combination with methotrexate, are recommended by NICE as options for treating RA, only if disease is severe and disease has not responded to intensive therapy with a combination of cDMARDs.

• Adalimumab, etanercept, certolizumab pegol or tocilizumab can be used as monotherapy for people who cannot take methotrexate because it is contra-indicated or because of intolerance. Treatment should be continued only if there is a moderate response measured using European League Against Rheumatism (EULAR) criteria at six months after
  starting therapy.⁸

• Adalimumab, etanercept, infliximab and abatacept can treat moderate RA after conventional DMARDs have failed.⁹
  

• Upadacitinib can also be offered as an option for patients who meet the same criteria as adalimumab as above.¹⁰

Following failure of TNF inhibitor treatment¹¹

• Rituximab in combination with methotrexate is recommended as an option for the treatment of adults with severe active RA who have had an inadequate response to, or are intolerant of, other DMARDs, including at least one TNF inhibitor. Treatment with rituximab should be given no more frequently than every six months.

• Adalimumab, etanercept, infliximab and abatacept, each in combination with methotrexate, are recommended as treatment options for adults with severe active RA who have had an inadequate response to, or have an intolerance of, other DMARDs, including at least one TNF inhibitor, and who cannot receive rituximab.

• Adalimumab monotherapy and etanercept monotherapy are recommended as treatment options for adults with severe active RA who have had an inadequate response to, or have an intolerance of, other DMARDs, including at least one TNF inhibitor, and who cannot receive rituximab therapy because they are unable to be treated with methotrexate.¹¹

• Tocilizumab in combination with methotrexate is recommended as an option for the treatment of rheumatoid arthritis in adults if:¹²

  • The disease has responded inadequately to DMARDs and a TNF inhibitor and the person cannot receive rituximab because of a contra-indication to rituximab, or because rituximab is withdrawn because of an adverse event.

  • The disease has responded inadequately to one or more TNF inhibitor treatments and to rituximab.

• Filgotinib can be used in combination with methotrexate, for the management of moderate to severe RA whose disease has responded inadequately to intensive therapy with two or more conventional DMARDs or rituximab; or cannot have other DMARDs or rituximab.¹³

Diet and complementary therapies

• There is no strong evidence that patients with RA will benefit from changes in diet.

• A Mediterranean diet should be encouraged (more bread, fruit, vegetables and fish; less meat; and replace butter and cheese with products based on vegetable and plant oils).³

• Complementary therapies may provide short-term symptomatic benefit but there is little or no evidence of long-term benefit.
  
  Advise RA patients who wish to try complementary therapies:

  • That they should not replace conventional treatment.

  • That this should not affect the care offered by any member of the MDT.

Annual review

Patients should be offered an annual review by a hospital specialist or GP with special interest to:³

• Assess disease activity and damage, and measure functional ability - using, for example, the Health Assessment Questionnaire (HAQ).

• Check for the development of comorbidities, such as hypertension, coronary heart disease, osteoporosis, and depression.

• Assess for complications, such as vasculitis and disease of the cervical spine, lung or eyes.

• Organise appropriate referrals within the MDT whenever appropriate.

• Assess the need for referral for surgery.

• Also, review the effectiveness and adverse effects of medication.

• Assess the effect the disease is having on the patient's personal life (for example, the capacity to work, study, mix socially and remain financially viable).

Surgery³

The opinion of an orthopaedic surgeon with a special interest in RA should be sought in patients who are on maximum tolerated therapy but have uncontrollable pain and/or significant restrictions of joint movement.

NICE guidance on referral for surgery

Refer people with RA for an early specialist surgical opinion if the following do not respond to optimal non-surgical management:

• Persistent pain (from, for example, joint damage or other soft tissue cause).

• Worsening joint function.

• Progressive deformity.

• Persistent localised synovitis.

Refer people with complications for a specialist surgical opinion before damage or deformity becomes irreversible:

• Imminent or actual tendon rupture.

• Nerve entrapment (for example, carpal tunnel syndrome).

• Any stress fracture.

Refer urgently for:

• Suspected or proven septic arthritis (especially in a prosthetic joint).

• Any symptoms or signs that suggest cervical myelopathy.

Do not let concerns about the long-term durability of prosthetic joints influence decisions to offer joint replacements to younger people with RA.