Rheumatoid Arthritis

Current Care Guidelines
Working group set up by the Finnish Medical Society Duodecim and the Finnish Society for Rheumatology
9.3.2017

Current Care Guideline in Finnish «Nivelreuma»1

Summary

  • A patient suspected of having rheumatoid arthritis (RA) should be referred without delay to a multi-disciplinary rheumatology clinic for confirmation of the diagnosis and treatment start.
  • If left untreated or if treated with inferior drugs, patients with RA will experience disease progression and the RA will become a crippling disease. Effective treatment, on the other hand, can prevent disease progression for most patients.
  • The goal of treatment of early RA is prompt and sustained disease remission, which allows the patient to recover and maintain his or her functional capacity and working ability.
  • Treatment of active RA is started with combination pharmacotherapy: methotrexate, sulfasalazine, hydroxychloroquine and a low dose of glucocorticosteroid (usually prednisolone 5.0–7.5mg or an equivalent glucocorticosteroid in the morning for at least 6 months), if there are no contraindications. The efficacy of monotherapy is poorer than of combination therapy.
  • Methotrexate is the anchor drug, onto which other antirheumatic drugs are added. If methotrexate is contraindicated, leflunomide or azathioprine may be used.
  • A glucocorticosteroid should be injected intra-articularly into inflamed joints.
  • If active RA does not respond to combination treatment, the disease should be treated with biologics.
  • Since RA is associated with an increased risk of bone fractures, prevention of osteoporosis is important.
  • The patient's risk for cardiovascular disease should be assessed as a part of overall disease assessment.
  • Patient education aims to ensure the compliance of the patient with long-term treatment.
  • Patients are encouraged to exercise and to maintain their muscle strength.
  • The multi-disciplinary team at the rheumatology clinic follows the patient's condition and disease activity, and when the RA has been in stable remission for a given period of time, e.g., two years, it is recommended that the patient visits annually a physician with a good understanding of rheumatology. ̣

Goals

  • The aim of these guidelines is to improve and harmonise the diagnosis and management of RA to ensure that the quality of life, the working capacity and the functional capacity of patients with RA are maintained.

Target groups

  • These guidelines are targeted at health care professionals at all levels (e.g., general practice, occupational health service and specialised care), who care for patients with inflammatory rheumatic diseases.

Epidemiology

Incidence and prevalence

Aetiology

Mortality

Diagnostic goals

Importance of early diagnosis

Signs and symptoms

  • Joint inflammation is the sine qua non for a diagnosis of RA. Usually there is inflammation in several joints.
  • The inflamed joint is typically swollen, stiff in the morning and painful on movement, but not necessarily painful at rest.
  • Symptoms usually start in the small and medium-sized joints (MCP, PIP, wrists and MTP joints), although any joint may herald the disease.
  • In typical cases, joint inflammation is symmetrical.
  • Joint symptoms usually develop slowly and progress gradually, often in a relapsing-remitting pattern. RA may cause inflammation in the cervical spine, but symptoms of the lower back are not characteristic of RA.
    • The more active the joint inflammation is, the longer is the duration of morning stiffness.
    • Joint inspection and palpation are important. The inflamed joint is swollen and usually tender on palpation. Clinical examination of the joints requires experience.
    • Joint erosions usually develop first in the MTP joints «Eroosiot ilmaantuvat ensin jalkateriin.»A. One of the therapeutic goals is to have the patient on antirheumatic pharmacotherapy before joint erosions and permanent damage develop.
    • The erythrocyte sedimentation rate (ESR) and the concentraton of C-reactive protein (CRP) in the serum or plasma reflect disease activity acceptably well, but are not always increased. In long-standing chronic disease, ESR may be permanently high «Sokka T, Pincus T. Erythrocyte sedimentation rate,...»41.
  • Approximately two thirds of patients with early RA are RF- or anti-CCP-positive «Möttönen T, Paimela L, Leirisalo-Repo M ym. Only h...»42. These findings are highly suggestive for RA, but are not a requirement for the diagnosis.
    • If the patient has no joint inflammation, testing for RF and anti-CCP is usually not indicated.
    • Joint inflammation of unknown aetiology requires synovial fluid analysis, if possible. The synovial fluid is analysed for cell count and differential count of white blood cells and crystals. If the joint aspirate is turbid, bacterial staining and culture are in order. In RA, synovial fluid is usually somewhat cloudy due to a high leukocyte count and its viscosity is reduced.
    • If the leucocyte count of the synovial fluid is above 2,000 x 106/l, the finding is compatible with inflammation and suggests RA or some other form of arthritis (Table «Synovial fluid analysis: interpretation...»1).
Table 1. Synovial fluid analysis: interpretation
Interpretation Leucocyte count (x 106/l)
Non-inflammatory < 2 000
Inflammatory 2 000–60 000
Strongly inflammatory > 60 000

Main diagnostic criteria

  • There are several international criteria for the classification of RA, and the most recent one has been published by an American/European expert panel (ACR/EULAR2010; interactive table in Finnish «http://www.terveysportti.fi/xmedia/hoi/hoi21010/Nivelreuman_luokittelukriteerit.html»1). The criteria put special emphasis on the presentce of polyarthritis and of RF or anti-CCP present in high titres. Although the criteria are intended for disease classification, they aid clinical decision making.

Diagnostic levels

  • A patient suspected of having RA should be referred without delay to a unit specialised in rheumatology where the services of a multidisciplinary team are available to confirm the diagnosis and start treatment.
  • The note of referral should include information on the patient's history, signs, symptoms and clinical examination, and the numerical values of the ESR, CRP, RF and anti-CCP.
  • Oral glucocorticosteroids may mask symptoms and compromise the diagnosis. Non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular glucocorticosteroid injections may be used to alleviate the sympotoms of the patient «Luosujärvi Riitta. Niveltensisäinen kortisonihoito...»43.
  • If RA or some other chronic rheumatic joint diseases are not suspected and the diagnosis is, e.g., gout, reactive arthritis or erosive osteoarthritis, patients can often be treated outside rheumatology units.
  • Local health care arrangements may slightly differ from the current recommendations. See tables «Evaluation of patient with arthritis...»2 and «Special features to consider in differential diagnostics....»3.
Table 2. Evaluation of patient with arthritis
Clinical picture Evaluation
A All patients with arthritis
Laboratory tests
  • ESR, CRP, blood count, urine, urate in men and postmenopausal women
  • Synovial fluid analysis (cell counts, crystals, stain and culture if needed)
History (*see point D)
  • Duration of morning stiffness, tenderness in movements, pains and aches, low back pain in rest, previous trauma
  • History of joint symptoms, family history of arthritis
  • Psoriasis (skin, nails), preceeding diarrhea*, inflammatory symptoms in eyes*, symptoms in urination, pass from urethra*, sex contacts*
  • Other infections (e.g., tonsillitis)
  • Raynaud's phenomenon
  • Solar dermatitis, MTP1 arthritis after use of beer or diuretics (see point B)
B Monoarthritis (gout, pseudogout, bacterial arthritis, reactive arthritis)
  • Joint aspiration (cell counts, crystals, stain and culture if needed), urate (may be normal in acute gout)
C Chronic/primarily arthritis primarily of the small joints (rheumatoid arthritis?)
  • rheumatoid factor (RF) and anti-cyclic citrullinated peptide (aCCP) antibodies
D Patients who have history positive for (*)-marked items in point A and sudden arthritis in a young individual (infection related arthritis, reactive arthritis)
  • Stool culture, antibodies against Yersinia, Salmonella and Campylobacter
  • Chlamydia-PCR from urine (or antigen test from urethra or cervix), gonococcus culture, if needed
  • Chlamydia-antibodies (high titre may occur long after the primary infection and therefore urine-PCR is preferred for sensitivity and specificity)
E Possible tick bite or erythema migrans, EM (history / current)
  • Borrelia burgdorferi antibodies; Negative antibodies in early disease (EM or arthralgia) do not exclude Lyme borreliosis.
  • Consider repeating the test after 1–2 months
  • Arthritis: synovial fluid borrelia-PCR confirms but negative result does not rule out diagnosis
Skin eruptions (pox)
  • Consider rubella
  • Sindbis-antibodies if itching dermatitis late August-September
  • Consider Erythema infectiosum
F Fever and tonsillitis prior to arthritis (rheumatic fever?)
  • Streprococcus culture in pharynx
  • EKG
Heart murmur, migrating polyarthritis, long PQ in ECG, pericarditis (rheumatic fever?)
  • AST (when clinical suspicion of rheumatic fever; negative result indicates that rheumatic fever is unlikely)
  • Cardiac sonography
  • Chest radiograph
Table 3. Special features to consider in differential diagnostics.
Diagnosis Special features
Osteoarthritis Pain that is worse after activity or towards the end of the day
Bony growths (‘spurs') 'around joints' (e.g. fingers: DIP, PIP joints)
Limited range of movement or stiffness that abates
Spondyloarthropathy / Arthritis Runs in family HLA-B27-associated in 60–80% of patients Low extremities, Enthesitis
Usually oligo-monoarthritis
Dactylitis (see Aikakauskirja Duodecim «http://www.terveysportti.fi/xmedia/duo/duo95528.pdf»2 and figures «Daktyliitti»1, «Daktyliitti»2 (in Finnish))
Polymyalgia rheumatica Pain and stiffness in buttocks, hips, thighs, upper arms and shoulders
Patient may have synovitis in knees, wrists
Patient cannot squat or lift up arms
Stiffness after rest or long periods of inactivity
Consider possiblility of giant cell arteritis
Virus arthritis Sudden onset
Usually poly- or oligoarthritis
Usually dermatitis
Usually in the fall
Gout Sudden onset of arthritis, usually at night
Usually monoarthritis
Signs of inflammation: pain, swelling and redness
Most often MTP1 affected
Risk factors: metabolic syndrome, diuretics
Also elderly women with osteoarthritis might have gout
Septic arthritis Systemic symptoms usual
Sudden monoarthritis usual
Oligoarthritis rare but possible
Lyme borreliosis Erythema migrans, EM may be absent
May start with arthralgias and myalgias, later monoarthritis (usually knee) or oligoarthritis
Effusion more prominent than pain
Dactylitis or tendinitis possible
Psoriasis Family history
DIP joint involvement typical but rare
Usually oligoarthritis but polyarthritis and spondyloarthritis possible
Skin involvement
Nail involvement
Dactylitis, e.g., sausage toe or sausage finger
Image 1.

Daktyliitti. © Markku Kauppi

Image 2.

Daktyliitti. © Markku Kauppi

Imaging

  • Imaging supports clinical examination by identifying joint inflammation and permanent damage.

Radiography

  • Radiography should be performed in radiology units that provide high quality images by appropriate techniques «Laasonen L. Tavanomainen röntgentutkimus perifeeri...»44.
  • Radiographs are taken of the hands and feet as part of the diagnostic work-up of RA and other peripheral inflammatory joint diseases. A chest radiograph should be taken for differential diagnostic purposes and also before immunosuppressive pharmacotherapy is initiated.
  • Serial radiographs of the hand and feet may be taken judiciously over time to document disease follow-up.
  • RA does not affect the spine, except the cervical part. In patients with severe and long-lasting RA, spinal subluxation may occur, best identified on flexion/extension lateral radiographs. In severe rheumatic spinal disease, in particular if the patient has atlanto-axial subluxation (AAS), there is a risk of spinal cord damage of the cervical spine, if the neck is moved into extreme positions. This needs to be taken into account prior to general anaesthesia (flexion/extension radiographs of the cervical spine should be taken preoperatively). Cervical subluxations (e.g., AAS) are most reliably identified in lateral radiographs taken during flexion of the neck. These lateral images are the most important images of the rheumatoid cervical spine.

Sonography

MRI

  • Of all modern imaging techniques, MRI provides the best anatomical images of the joints and the periarticular soft tissue «Magneettikuvaus on paras kuvantamismenetelmä nivelreuman aiheuttamien muutosten toteamisessa.»A.
  • Contrast agents aid in the detection of active synovitis and enable earlier detection of erosions than conventional radiographs.
  • MRI is not usually needed for diagnostic or monitoring purposes. Unequivocal indications for MRI are differential diagnostic problems.
    • In severe disease of the cervical spine, MRI should be performed. Subluxations are identified by plain extension/flexion radiographs of the cervical spine. If displacement of the cervical vertebrae are seen, the effect of these anatomical changes are to be taken into account when the MRI images are interpreted to document any compression of the neural structures and spinal cord.

Treatment of RA

Early treatment of RA

Rehabilitation

  • Physical exercise as a form of rehabilitation has the strongest impact on the patient's functional capacity.
  • Rehabilitation, as well as pharmacotherapy, aims at enhancing the patient's functional capacity, working ability and overall wellbeing.
  • Pharmacotherapy and rehabilitation complement each other: the need for rehabilitation is often minimized, if active pharmacotherapy restores the patient's functional capacity.
  • WHO's ICF-classification (International Classification of Functioning, Disability and Health) «http://www.who.int/classifications/icf/en/»4 provides a framework for rehabilitation measures which may be applied to the patient herself or himself as well as to the physical or social environment of the patient.

Medical rehabilitation

Vocational rehabilitation

  • The goal of vocational rehabilitation is to support the employment of disabled subjects by developing their professional skills and working environment.
  • The patient's potential to retain his or her working capacity has to be assessed no later than after 90 weekdays of sickness allowance. This assessment is documented on a statement by the occupational health care physician. If the patient does not have the benefit of occupational health care services, the consultation of the employment office (TE-services) or the SII must be sought to assess the patient's possibilities for vocational rehabilitation. In addition, a multidisciplinary rehabilitation meeting arranged at a rheumatology or rehabilitation clinic may be helpful.
  • Referral to vocational rehabilitation requires a plan for rehabilitation, i.e., a statement made by the treating physician. For continuously employed patients, the pension insurance company takes on the responsibility for the rehabilitation costs, otherwise the SII is the payor.
  • Vocational rehabilitation is most beneficial when the subjects is threatened by disability or when work disability has been only temporary «Ammatillinen kuntoutus turvaa työkykyä todennäköisimmin silloin, kun kyseessä on työkyvyttömyyden uhka tai työkyvyttömyys on ollut tilapäistä.»B.

Ongoing rheumatoid arthritis treatment

  • There is no curative treatment for RA. Pharmacotherapy is usually continued for years or decades, because RA symptoms tend to relpse on discontinuation of treatment. For patients who have remained asymptomatic for years, medication can be decreased but close observation must be maintained.
  • 10–15% of patients with RA achieve sustained remission where no medication is needed «Nivelreumapotilaista 10–15 % voi päästä pitkäaikaiseen lääkkeettömään remissioon.»A.
  • The patient with RA should visit annually a physician who has a good understanding of treatment of RA.
  • If the medication has been reduced and the RA relapses, the pharmacotherapy to which the patient previously responded is re-introduced or dosages increased.
    • Subcutaneous or oral methotrexate may be re-introduced, even if it was discontinued after previous use, since discontinuation is often due to an ineffective dose or mild adverse events.
    • If there are no contraindications, the RACo-combination is introduced: methotrexate, sulfasalazine, hydroxychloroquine and a low-dose glucocorticosteroid (usually prednisolone 5.0–7.5mg daily or equivalent).
    • Leflunomide may be also used.
  • If the response to methotrexate-based combination treatment poor or absent, the RA is treated with biologics.
  • In long-lasting disease, triple combination therapy gives comparable results to treatment with biologics in patients who have responded inadequately to methotrexate monotherapy «Pidempäänkin kestäneessä nivelreumassa perinteinen yhdistelmähoito on biologisen lääkityksen veroinen potilailla, jotka eivät ole saaneet riittävää vastetta metotreksaatille.»A.

Pharmacotherapy of rheumatoid arthritis

Conventional synthetic disease modifying drugs (csDMARDs)

Table 4. Methotrexate (MTX), special aspects
Dose First dose 10–15mg sc or po
Second dose of MTX is the maintenance dose a week later «Bykerk VP, Akhavan P, Hazlewood GS ym. Canadian Rh...»115
Recommended maintenance dose in the beginning of treatment is 20–25mg once a week.
Later on, maintenance dose will be tailored for each individual, balanced between side effects and benefits.
Side effects Usual:
GI-tract, nausea, dizziness, hair loss, stomatitis, elevated liver enzymes, increased red cell volume
Rare:
Interstitial lung disease, cytopenias
Interactions Trimetoprim, probenecid
Contraindications Pregnancy and breast feeding
No need to interrupt MTX when planning fathering «Malm H. Isän kautta välittyvä teratogeneesi - aihe...»53
With caution Compromized kidney function (creatinine clearance < 60ml/min) «The effect of age and renal function on the effica...»52, liver diseases, lung fibrosis
Beneficial combination with Hydroxychloroquine + sulfasalazine, bDMARDs, cyclosporine
Other aspects "Anchor" drug
Bioavailability best sc or im vs po
Folic acid (5mg/week e.g. following day) improves tolerability and safety
If the serum aminotransferase increases to a level x 3 above the reference value, examinations are needed.
If no other reasons except MTX, establish highest dose that the patient tolerates.
Table 5. Sulfasalazine (SSZ), special aspects
Dose Begin 500mg × 2, after 1–2 weeks increase to 1 g × 2.
Side effects Usual:
GI-tract, mild CNS symptoms, oligospermia that resolves after discontinuation of SSZ, decreased sperm motility
Rare:
Severe skin reaction
Severe cytopenias
Interactions May decrease absorption of digoxin
Contraindications Hypersensitivity to sulfonamids and salicylates
Beneficial combination with Methotrexate + hydroxychloroquine Intramuscular gold (=natriumaurothiomalate)
Other aspects Part of triple combination
Can be used during pregnancy and breast feeding
Folic acid is recommended during pregnancy.
Table 6. Hydroxychloroquine (HCQ), special aspects
Dose About 5mg/kg/day
Side effects Usual:
GI-tract, mild CNS symptoms, nightmares, solar sensitivity Rare: Retinopathy, myopathy, kardiomyopathy
Interactions -
Contraindications Maculopathy of the eye
Beneficial combination with Intramuscular gold (=natriumaurothiomalate)
Methotrexate and sulfasalazine
Other aspects Part of triple combination
Can be used during pregnancy and breast feeding
A baseline examination by an ophthalmologist and after 5 years of use «Marmor MF, Kellner U, Lai TY ym. Revised recommend...»114
Table 7. Leflunomide, special aspects
Dose 20mg x 1/day (if issues of tolerability, 20mg every other day)
Side effects Diarrhea, reversible hair loss, dermatitis, headache
Interactions Rifampicin (increases concentration)
Contraindications Liver disease, pregnancy
Other aspects If aminotransferase levelös increase 2–3 times above normal, careful follow-up is indicated. If levels remain high, discontinue leflunomide and consider cholestyramine to wash out leflunomide.
Pay special attention to young women, as leflunomide may delay plans for pregnancy due to long withdrawal time of leflunomide
Table 8. Cyclosporine, special aspects
Dose Initial dose 2.5–3mg/kg/day, not >4mg/kg/day
Side effects Usual:
Increased hair growth, tremor, decreased kidney function, increased blood pressure, gingival overgrowth, GI-tract, paresthesia
Interactions Following drugs increase cyclosporin concentration:
Erythromycin, doxycycline, some antifungal drugs, calcium blockers, propaphenon, H2-blockers, metoclopramide, oral contraceptives and St. John’s wort (Hypericum perforatum)
Following drugs decrease cyclosporin concentration: Barbiturates, carbamazepine, phenytoin, metamizole, rifampicin, nafcillin, trimethoprim (i.v.), sulfoamides (i.v.)
Contraindications Malignancy, uncontrolled hypertension, compromized kidney function, immunodeficiency, pregnancy, breast feeding
Beneficial combination with Methotrexate
Other aspects If aminotransferase levelös increase 2–3 times above normal, careful follow-up is indicated. If levels remain high, discontinue leflunomide and consider cholestyramine to wash out leflunomide.
Pay special attention to young women, as leflunomide may delay plans for pregnancy due to long withdrawal time of leflunomide
Table 9. Intramuscular gold (natriumaurothiomalate), special aspects
Dose Intramuscular: after 10mg dose, 50mg weekly until a cumulative dose of 13mg/kg
Maintenance dose 50mg every 1–4 weeks
Side effects Usual:
Skin reactions, stomatitis, proteinuria
Rare:
Cytopenias, interstitial lung disease Polyneuropatia
Interactions
Contraindications Cytopenias, kidney or liver disease, pregnancy (3rd semester allowed)
Beneficial combination with Methotrexate
Hydroxychloroquine
Other aspects Proteinuria indicates membranous glomerulonefritis and treatment needs to be discontinued.
Table 10. Azathioprine, special aspects
Dose First week 50mg/day, thereafter 2–2.5mg/kg/day divided in 2–3 doses
Side effects Usual:
GI-tract, nausea, elevated aminotransferases
Rare:
Severe cytopenias
Interactions Allopurinol (life-threatening interaction)
Contraindications Pregnancy and breast feeding (relative contraindication)
Beneficial combination with
Other aspects Constantly elevated aminotransferases
Table 11. Azathioprine, special aspects
Dose 1–2 g/day, divided in two doses
Side effects Usual:
Nausea, diarrhea, stomach pain, infections, cytopenias
Rare:
Increased aminotransferases, decreased kidney function
Interactions Rifampicin, rifamycin
Contraindications Pregnancy and breast feeding
Beneficial combination with
Other aspects Live vaccines not recommended
Risk of skin cancer is increased
Table 12. Cyclophosphamide, special aspects
Dose 1.5–2.5mg/kg/day, divided in 2–3 doses, po
Side effects Usual:
GI-tract, cytopenias, infections, infertility
Rare:
Secondary malignancy
Interactions
Contraindications Susceptibility to infections, pregnancy, breast feeding
Beneficial combination with
Other aspects May be needed in systemic manifestations
Table 13. Pennicillamine, special aspects
Dose Initial dose 125mg × 1/day; increase by 125mg / 4 weeks until 500–600mg/day
Side effects Usual:
Skin reactions, stomatitis, taste disturbance, proteinuria
Rare:
Cytopenias, myasthenia gravis, polymyositis, SLE, Goodpasture's syndrome, pemphigus
Interactions
Contraindications Decreased kidney function
Pregnancy, breast feeding
Beneficial combination with -
Other aspects Needs special permit from Finnish Medicines Agency (Fimea)
Proteinuria indicates membranous glomerulonephritis and treatment needs to be discontinued.
Due to difficult dosage and side effects (especially dysgeusia) is rarely used nowadays

Biologic disease modifying drugs (bDMARDs)

Table 14. bDMARDs
Generic product Group Mode of action Half life Route of admin Dose Attention
Adalimumab TNF-α blocker Human monoclonal antibody 10–18 days sc 40mg every two weeks
Etanercept TNF-α blocker p75 receptor fusionprotein 3 days sc 50mg once a week or 25mg twice a week
Sertolitsumabpegol TNF-α blocker PEGylated Fab' fragment of a humanised TNF inhibitor monoclonal antibody 14 days sc 200mg every 2 weeks or 400mg once a month Starting dose to adults 400mg at weeks 0, 2, 4
Golimumab TNF-α blocker Human monoclonal antibody 9–15 days sc 50mg once a month If insufficient efficacy and patient's weight >100 kg, dose increase: 100mg once a month
Infliksimab TNF-α blocker Chimeric, monoclonal antibody 10 days iv 3mg/kg in weeks 0, 2, 6, thereafter every 8 weeks
Rituksimab B-cell inhibitor CD20 chimeric, monoclonal antibody 3–4 days iv 500–1 000mg 2 weeks apart, repeated after 6–12 months IgG levels at baseline and before every infusion

Infection and malignancy risk of biologics

TNF-α blockers

Interleukin 1 inhibitor (anakinra)

Interleukin 6 inhibitor (tocilizumab)

B-cell blocker (rituximab)

T-cell blocker (abatacept)

Glucocorticosteroids

Non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics

Prevention of osteoporosis

  • The rheumatic inflammation and glucocorticosteroid treatment subject the patient to secondary osteoporosis. Glucocorticosteroids increase the risk of osteoporosis dose-dependently and the risk of fractures. Therefore, prevention of osteoporosis is important for patients on pharmacotherapy for RA (Current Care Guidelines of osteoporosis «Osteoporoosi»3 in Finnish).

Addressing the atherosclerosis risk

The impact of diet on rheumatoid symptoms

  • Special dietary interventions are not recommended for the treatment of RA. The effect of specific dietary regimens (vegetarian, Mediterranean, elemental, elimination diets) on the symptoms of RA (pain, stiffness, function) is uncertain «Hagen KB, Byfuglien MG, Falzon L ym. Dietary inter...»100. Studies have been small and their reliability affected by systematic errors of study designs.

Rheumatoid orthopaedic surgery

  • The goal of active anti-rheumatic medication is to obviate the need for operative treatment.
  • Statistics show that rheumaorthopaedic operations have declined notably during last 20 years due to more effective medication «Jämsen E, Virta LJ, Hakala M ym. The decline in jo...»102. Patients with chronic RA may have joint changes which may be relieved with orthopaedic surgery «Matti U.K. Lehto. Reumaortopedian valtakunnallinen...»103.
  • Synovectomy (today usually arthroscopic synovectomy) is indicated, if the inflammation in a single joint continues despite active anti-rheumatic pharmacotherapy. Synovectomy relieves often joint pain and stiffness. Postoperatively, effective anti-rheumatic pharmacotherapy should be continued to prevent re-synovitis. If the cartilage surface of the joint is in poor condition before synovectomy, the operative result may be poor or brief. A treatment option for "drug-therapy refractory synovitis" of the knee joint is radiosynovectomy, where a short-lived radionuclide is injected into the knee joint and removed after a while. This option is available only in some university hospitals in Finland.
  • Tenosynovitis and nodules in the tendons refractory to conservative therapy limit the movement of joints and may be treated surgically with tenosynovectomy. If tenosynovectomy is done to the flexor tendons of the wrist, the carpal canal is usually also opened and the median nerve liberated «Simmen BR, Bogoch ER, Goldhahn J. Surgery Insight:...»104.
  • Arthrodesis may relieve the pain of a severely destroyed joint and improve function of the whole extremity. Arthrodeses may correct severe deformities and prevent the progression of deformities. Usually, arthrodeses are performed in the wrist, subtalar joint, first metatarsophalangeal joint and sometimes in the finger joints.
  • Severe deformity in the cervical spine may be an indication for operative treatment. Severe anterior atlanto-axial subluxation (AAS) is usually treated surgically by fusing vertebrae C1 and C2.
  • The results of total hip and knee arthroplasties are good «Simmen BR, Bogoch ER, Goldhahn J. Surgery Insight:...»104. The prosthesis type for glenohumeral arthroplasty is selected individually. For patients with a severly degenerated rotator cuff, a reverse shoulder arthroplasty prosthesis is often used, because then the shoulder muscles may compensate for the loss of rotator cull function and generate satisfactory ranges of movement. The 10-year survival rate of prostheses of the large joints is 85–95% «Ikävalko M. Rheumatoid Elbow Destruction and its T...»105.
  • Prosthesis of the ankle, wrist and fingers may be used in selected RA cases.
  • Rheumaorthopaedic revision operations are often challenging «Simmen BR, Bogoch ER, Goldhahn J. Surgery Insight:...»104.
  • Painful rheumatoid nodules and bursae may require operative treatment.
  • The postoperative infection risk of patients with RA is elevated if the patient has certain concomitant diseases, like diabetes, impaired circulation in the operated limb and a history of infections after previous operations.
  • DMARDs, and especially biologics, often increase the risk of infections, which has to be taken into account when the surgical risks are evaluated. The biologics may be paused before and after an operation, depending on the patient and the DMARDs. The downside of discontinuing antirheumatic pharmacotherapy are, however, an increased risk of rheumatoid flare, an impaired surgical outcome and even an increased risk of infection. There is an abundant literature on how to discontinue antirheumatic pharmacotherapy before surgery, but strong evidence for the benefit of such a discontinuation is lacking. In general, it is reasonable to withhold biologics for 1–2 weeks before surgery and for the time after surgery until the surgical wound shows signs of good primary healing. Biologics need not be discontinued for minor, clean operations.

Patient education

  • Patient education improves compliance with drug treatment «Hill J, Bird H, Johnson S. Effect of patient educa...»106 and improves the patient's state of health, at least in the short term «Potilasohjaus vaikuttaa ainakin lyhyellä tähtäimellä edullisesti nivelreumapotilaiden terveydentilaan.»A.
    • The treatment of RA is based on a shared decisions between the patient and the treating physician. This presupposes that the patient knows the risks and benefits of the intended treatment «Smolen JS, Aletaha D, Bijlsma JW ym. Treating rheu...»107.
    • The role of the rheumatology nurse for efficient patient education is crucial.
  • The patient needs to understand:
    • the nature of RA and how it progresses, if untreated
    • how RA is treated
    • that remission is a realistic target in early disease and that stringent adherence by the patient to the prescribed medication is important
    • that the medication might have side effects and patients may need to switch medications, but the risks of having RA untreated are manyfold compared to the risks of the medication.
  • Smoking is a risk for RA.
  • Patient education needs to be comprehensive, well-structured and comprehensive. A supportive attitude of the treating physician and the rheumatology nurse is essential.
  • A physiotherapist should provide education on physical exercise.
  • As needed, the patient should be referred to an occupational therapist, podiatrist, dietician, psychotherapist or social worker.
  • The patient needs to have an assigned health care professional as a contact person.
  • Patient education may be provided following the motivational interview strategy «Lahti J, Maria R, Koski-Jännes A. Motivoiva haasta...»108. [HUOM! Motivoiva keskustelu; lisätäänkö linkki Oppiporttiin?]
  • Treatment pathway. [HUOM! Tässä kohtaa on suomenkielisessä suosituksessa linkki powerpoint-esitykseen]

Patient follow-up

  • We recommend that each rheumatology unit follows a clinical pathway for the care of patients with early RA. The objectives of following such a pathway are to guarantee that:
    • the patient starts the medication agreed on
    • possible adverse events are balanced against effective drug treatment
    • the treatment target is remission during the first few months of treatment
    • remission is sustained.
  • When the RA-patient attends for follow-up, disease activity is measured with the following scales:
  • The recommendation is to take radiographs of the hands and feet at baseline (at the time of diagnosis), at the two-year follow-up visit and thereafter as dictated by the patient's symptoms.
  • This working group recommends that the rheumatology unit ensures sustained remission for up to two years. Following this, the patient should have annual follow-up visits at a physician with a good understanding of rheumatology «Aktiivinen ote nivelreumapotilaan hoitoon parantaa merkitsevästi hoitotulosta.»A.
  • Blood tests for drug safety should be taken and assessed by a physician in primary care.
  • For use of medication during pregnancy and lactation see GRAVBASE-database «http://www.terveysportti.fi/terveysportti/dlv.koti?p_kielikoodi=fi&p_sovellustunnus=RI&p_mainos=E»11 (in Finnish, only for subscribers).
  • The risk of infection must be considered when biologics are used and appropriate vaccinations need to be guaranteed.
  • Close collaboration between the rheumatology unit and primary care is crucial since treatment of RA will go on for years and decades.
  • If the overall treatment is to be successful, relapses of RA must be recognised in primary care.
  • The patient is referred to a rheumatologist, if the relapse is not adequately controlled by the measures provided by the "toolbox" (see Table «GP's tool box...»15).
Table 15. GP's tool box
GP's tool box:
RA flares, what to do:
  • Mono/oligoarticular flare > intra-articular glucocorticosteroid injections
  • Dose increase of csDMARD
  • Low dose systemic glucocorticosteroid as a bridging therapy (5.0–7.5mg/day)
  • Confirm adequate response to therapy
  • If inadequate response, consultation of a rheumatologist
Increased symptoms without signs of RA activity:
  • Examine and treat underlying factors for pain
  • Optimize pain medications
  • Physiotherapy and other non-pharmacological therapies
  • Devices

Cost-effectiveness of the pharmacotherapy of RA

  • RA incurs high societal costs, including direct costs from increased health care resource use and indirect costs from reduced work productivity.
  • The early treatment outcome of RA is strongly predictive of direct and indirect costs «Puolakka K, Kautiainen H, Mottonen T ym. Use of th...»109, «Hallert E, Husberg M, Skogh T. 28-Joint count dise...»110. Early remission ensures maintained working capacity «Puolakka K, Kautiainen H, Möttönen T ym. Early sup...»49.
  • A good early treatment outcome, remission at best, prevents high costs and enhances the patient's quality of life.
  • If the activity of RA continues unabated, the patient is at risk of joint damage, loss of function and loss of working capacity. Work productivity costs have long since been the major part of the total costs «Kobelt G, Eberhardt K, Jönsson L ym. Economic cons...»111.
  • If conventional synthetic anti-rheumatic pharmacotherapy is not effective, even an expensive medication is cost-effective if it prevents disability and early work incapacitation and retirement.
  • Costs due to work incapacity are reduced also if pharmacotherapy is upgraded later during the disease process, if this allows the patient to regain his or her functional capacity to a level compatible with the requirements of the patient's assignments «Augustsson J, Neovius M, Cullinane-Carli C ym. Pat...»112.
  • Several studies have shown that the functional capacity of RA patients has, on average, improved in the past two decades. For those diagnosed with RA after the turn of millennium, the risk of work disability is smaller than for those diagnosed before than «Rantalaiho VM, Kautiainen H, Järvenpää S ym. Decli...»113.
  • There are several studies on the cost-effectiveness of different medications and combinations, but usually they have been comparisons between methotrexate monotherapy and other pharmacotherapeutic regimens in cases of methotrexate failure. They are not relevant for Finnish practice. Comparisons of various biologics have been based on short-term treatment studies, and the patient cohorts have not often been comparable.

Working group appointed by the Finnish Medical Society Duodecim and the Finnish Society for Rheumatology

Chair:

Kari Puolakka, MD, PhD, Adjunct professor, Specialist in Internal Medicine and Rheumatology, South Karelia Social and Health Care District (Eksote), Head of Department; Lappeenranta

Members:

Markku Hakala, MD, PhD, Adjunct professor, Specialist in Internal Medicine and Rheumatology; Tampere

Markku Kauppi, MD, PhD, Specialist in Internal Medicine and Rheumatology, Professor, Head of the rheumatology unitUniversity of Tampere and Päijät-Häme Central Hospital,Lahti, Finland.

Eero Mervaala, MD, PhD, Professor, University of Helsinki, Faculty of Medicine, Department of Pharmacology and FInnish Medical Society Duodecim (Current Care Editor)

Laura Pirilä, MD, PhD, Adjunct professor, Specialist in Internal Medicine, Geriatrics and Rheumatology; Head of Deparment of Rheumatology, Turku University Hospital, Division of Medicine, Hospital District of Southwest Finland

Tuulikki Sokka-Isler, MD, PhD, Professor, Specialist in Internal Medicine and Rheumatology, Head of Department; Central Finland Central Hospital and University of Eastern Finland

Klaus Suni, MD, Specialist in General Practise, health centre physician; Health Care Centre of the Jyväskylä Region

Consultant:

Raine Tiihonen, MD, PhD, Specialist in orthopedics and traumatology, Head of Department; Päijät-Häme Cental Hospital, Lahti, Finland

Disclosures

Markku Hakala: Grant (Pirkanmaa Hospital District), Consultanting fees (Finnish Rheumatism Association), membersip of a board or equal (Finnish Rheumatism Association), Speaking fees (MSD, Fysioline, GSK), License royalties (Duodecim)

Markku Kauppi: Consultanting fees (AbbVie, BMS, Berlin Chemie Menarin, MSD, Pfizer, Roche, UCB), Speaking fees (AbbVie, BMS, Berlin-Chemie Menarini, GSK, MSD, Pfizer, Roche, Sanofi, UCB), Reimbursement for attending meetings (BMS, Berlin-Chemie Meniarini, MSD, Pfizer, UCB)

Eero Mervaala: Consultanting fees (Kustannus Medicina Oy), Employment (Yhtyneet Medix Laboratoriot), Speaking fees (Pharmaceutical Information Centre Ltd)

Laura Pirilä: Consultanting fees (Pfizer Oy), Speaking fees (AbbVie oy, Bristol-Myers Squibb (Finland), GlaxoSmithKline OY, Labquality Days/Labquality oy, Pfizer Oy, Pohjois-Savon sairaahoitopiiri, Roche oy, the Scandinavian Neuropathological Society, the Finnish Society for Rheumatolgy, University of Turku, Turunmaan Duodecim ry, UCB Pharma Oy Finland), Reimbursement for attending meetings (Actellion Pharmaceuticals Finland, Bristol Myer Squibb Finland, Roche Oy, UCB Pharma Oy Finland)

Kari Puolakka: Grant (Pfizer), Consultanting fees (Abbvie, Bristol-Myers Squibb, MSD, Pfizer, Roche, UCB), Speaking fees (Bristol-Myers Squibb, Pfizer, UCB), Reimbursement for attending meetings (Bristol-Myers Squibb, Pfizer, Roche)

Tuulikki Sokka-Isler: Grant (Abbvie, Hospira, Pfizer), Consultanting fees (Hospira, Novartis, Orion, Pfizer, UCB), Speaking fees (Abbvie, BMS, Hospira, MSD, Medac, Pfizer, Roche, UCB)

Klaus Suni: Reimbursement for attending meetings (MSD, Pfizer)

Translation

Elena Nikiphorou MBBS/BSc, MRCP, PGCME, MD (Res), FHEA

Tuulikki Sokka-Isler

Laura Pirilä

Markku Hakala

Kari Puolakka

Language revision:

MediDocs Ltd, Robert Paul

Limitation of responsibility

The clinical practice guidelines of the Finnish Medical Society Duodecim are summaries on the diagnostics and effectiveness of therapy on single diseases and are produced by experts. They do not replace the judgement of a physician or other healthcare specialist on the best possible diagnostics and therapy of an individual patient.

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