Guidelines Summary
Disease Classification
The 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA are designed to identify patients with unexplained inflammatory arthritis in at least 1 peripheral joint and a short duration of symptoms who would benefit from early therapeutic intervention. They represents a paradigm shift from the 1987 ACR criteria, which lacked the sensitivity to detect early RA. [1]
According to the ACR/EULAR criteria, patients who should be tested are those with at least 1 joint with definite clinical synovitis that is not better explained by another disease (eg, lupus, psoriatic arthritis, or gout). [1]
The ACR/EULAR classification system is a score-based algorithm for RA that incorporates the following 4 factors:
-
Joint involvement
-
Serology test results
-
Acute-phase reactant test results
-
Patient self-reporting of the duration of signs and symptoms
The maximum number of points possible is 10. A classification of definitive RA requires a score of 6/10 or higher. Patients with a score lower than 6/10 should be reassessed over time. If patients already have erosive changes characteristic of RA, they meet the definition of RA, and application of this diagnostic algorithm is unnecessary. [1]
Disease Activity Measures
In 2012, the ACR published revised recommendations for the measurement of disease activity for clinical use at the point of care. The scales used included the following recommended measures [2] :
-
Patient-driven composite tools – PAS (patient activity scale): scale, 0-10; PAS II: scale, 0-10; RAPID-3 (routine assessment of patient index data with 3 measures): scale, 0-10
-
Patient and provider composite tool – CDAI (clinical disease activity index): scale, 0-76
-
Patient, provider, and laboratory composite tools – DAS28 (28-joint disease activity score, using either the erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP] level): scale, 0-9.4; SDAI (simplified disease activity index): scale, 0-86
The 6 measures above result in a single continuous index with defined ranges for low, moderate, or high disease activity or clinical remission. [2] See Table 3, below.
Table 3. Rheumatoid Arthritis Disease Activity Cutoffs (Open Table in a new window)
Tool Type |
Tool |
Low/Minimal Disease |
Moderate Disease |
High/Severe Disease |
Patient-driven composite |
PAS, PAS |
0.26–3.70 |
3.71 to < 8.0 |
8.00–10.00 |
PASII |
0.26–3.70 |
3.71 to < 8.0 |
8.00–10.00 |
|
Patient and provider composite |
RAPID-3 |
>1.0–2.0 |
>2.0–4.0 |
>4.0–10 |
Patient, provider, and laboratory composite |
CDAI |
2.8–10.0 |
>10.0–22.0 |
>22.0 |
DAS28 |
2.6 to < 3.2 |
3.2–5.1 |
>5.1 |
|
SDAI |
>3.3–11.0 |
>11.0 to 26 |
>26 |
|
PAS= Patient Activity Scale; RAPID-3 = Routine Assessment of Patient Index Data with 3 measures; CDAI = Clinical Disease Activity Index; DAS28 = 28-joint Disease Activity Score (with either erythrocyte sedimentation rate or C-reactive protein level); SDAI = Simplified Disease Activity Index |
||||
Measurement of disease remission
In the 2012 ACR-recommended RA disease activity measures, the following cutoffs indicate disease remission [2] :
-
PAS and PAS-II: 0.00-0.25
-
RAPID-3: 0-1.0
-
CDAI: ≤2.8
-
DAS28 (ESR or CRP): < 2.6
-
SDAI : ≤3.3
In 2011, the ACR and the EULAR jointly released two definitions for evaluating remission of RA in clinical trials, one a Boolean-based definition and the other based on a composite index of RA activity, the SDAI. The Boolean-based definition requires that the patient satisfy all of the following to be considered in remission [3] :
-
Tender joint count of 1 or less
-
Swollen joint count of 1 or less
-
CRP level of 1 mg/dL or lower
-
Patient global assessment of 1 or less (on a 0-10 scale)
To be considered in remission using the traditional index definition, the patient must have an SDAI score of less than 3.3. [3]
Treating to Therapeutic Target
The following revised guidelines on treating RA to therapeutic target were issued in 2015 by an international task force of rheumatologists, patient representatives, and a rheumatology nurse [7, 8] :
-
The primary target for treatment of RA should be a state of clinical remission. (Level of evidence: Ib; grade of recommendation: A) which is defined as the absence of signs and symptoms of significant inflammatory disease activity. (Level of evidence: IIc; grade of recommendation: B)
-
While remission should be a clear target, low-disease activity may be an acceptable alternative therapeutic goal, particularly in long-standing disease. (Level of evidence: Ib; grade of recommendation: A)
-
The use of validated composite measures of disease activity, which include joint assessments, is needed in routine clinical practice to guide treatment decisions. (Level of evidence: Ib; grade of recommendation: A)
-
The choice of the (composite) measure of disease activity and the target value should be influenced by comorbidities, patient factors, and drug-related risks. (Level of evidence: IV; grade of recommendation: D)
-
Measures of disease activity must be obtained and documented regularly—as frequently as monthly for patients with high/moderate disease activity or less frequently (eg, every 6 mo) for patients in sustained low-disease activity or remission. (Level of evidence: Ib; grade of recommendation: A)
-
Structural changes and functional impairment and comorbidity should be considered when making clinical decisions, in addition to assessing composite measures of disease activity. (Level of evidence: IV; grade of recommendation: D)
-
Until the desired treatment target is reached, drug therapy should be adjusted at least every 3 mo. (Level of evidence: Ib; grade of recommendation: A)
-
The desired treatment target should be maintained throughout the remaining course of the disease. (Level of evidence: IIc; grade of recommendation: B)
-
The rheumatologist should involve the patient in setting the treatment target and the strategy to reach this target. (Level of evidence: IV; grade of recommendation: D)
Management of Early RA
In 2016, the European League Against Rheumatism (EULAR) updated its 2007 guidelines for the management of early arthritis, which put renewed emphasis on early intervention, preventive lifestyle measures, and careful clinical examination rather than reliance on ultrasound or advanced imaging. Key recommendations, based on evidence and expert opinion, are as follows [163] :
-
Within 6 weeks of the onset of symptoms, patients presenting with joint swelling associated with pain or stiffness should be referred to a rheumatologist (Level of evidence: Ib; grade of recommendation: B)
-
Clinical examination is the method of choice for detecting arthritis, which may be confirmed by ultrasonography (Level of evidence: IIb; grade of recommendation: C)
-
Patients should be started on disease-modifying antirheumatic drugs (DMARDs) as early as possible (ideally within 3 months), even if they do not fulfill classification criteria for an inflammatory rheumatologic disease (Level of evidence: Ia; grade of recommendation: A)
-
Methotrexate (MTX) is the preferred DMARD, unless contraindicated, and should be first-line treatment (Level of evidence: Ia; grade of recommendation: A)
-
Systemic glucocorticoids should be used at the lowest dose necessary as temporary (< 6 months) adjunctive treatment to reduce pain, swelling, and structural progression. Intra-articular glucocorticoid injections should be considered for the treatment of local symptoms of inflammation (Level of evidence: Ia; grade of recommendation: A)
-
Regular monitoring of disease activity, adverse events and comorbidities should guide decisions on choice and changes in treatment strategies to reach clinical remission (Level of evidence: Ib; grade of recommendation: A)
-
Arthritis activity should be assessed at intervals of 1 to 3 months until clinical remission has been reached. Monitoring should include tender and swollen joint counts, patient and physician global assessments, erythrocyte sedimentation rate, and C-reactive protein; radiographic and patient-reported outcome measures, such as functional assessments, can be used as complementary monitors. (Level of evidence: Ia; grade of recommendation: A)
-
Nonpharmacological interventions, such as dynamic exercises and occupational therapy, should be considered as adjuncts to drug treatment (Level of evidence: Ia; grade of recommendation: B)
-
Smoking cessation, dental care, weight control, assessment of vaccination status, and management of comorbidities should be included in overall patient care (Level of evidence: IIb; grade of recommendation: C)
-
Education programs aimed at coping with pain, disability, maintenance of ability to work, and social participation may be used as adjunct interventions (Level of evidence: Ia; grade of recommendation: B)
In its 2015 revised guidelines for the management of RA, the American College of Rheumatology (ACR) included the following recommendations for treatment of early RA [4] :
-
A treat-to-target stategy should be used regardless of disease activity. (Strong recommendation)
-
Low disease activity: DMARD monotherapy over double or triple therapy. MTCX is the preferred DMARD. (Strong recommendation)
-
Moderate or high disease activity: DMARD monotherapy over double or triple therapy. (Conditional recommendation)
-
Moderate /high disease activity despite DMARD monotherapy: Combination DMARDs or a tumor necrosis factor (TNF) inhibitor or a non-TNF biologic agent (Strong recommendation)
A change from 2012 to 2015 guidelines is that the 2015 guidelines do not recommend initial combination DMARD therapy in early RA with moderate to high disease activity.
Management of Established RA
Guidelines for pharmacologic therapy for RA have been issued by the following organizations:
-
European League Against Rheumatism (EULAR) [5]
The 2019 update of the EULAR RA management guidelines includes the following key recommendations for pharmacologic therapy [5] :
-
Therapy with disease-modifying antirheumatic drugs (DMARDs) should be started as soon as the diagnosis of RA is made.
-
Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient.
-
Patients with active disease should have frequent monitoring (every 1–3 months); if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted.
-
Methotrexate (MTX) should be part of the first treatment strategy.
-
In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the first-line treatment strategy.
-
Short-term glucocorticoids should be considered when initiating or changing the dose of a conventional synthetic DMARDs (csDMARD); different dose regimens and routes of administration may be used for glucocorticoids, but the drugs should be tapered as rapidly as clinically feasible.
-
If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors, other csDMARDs should be considered.
-
If the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present, a biologic DMARD or a targeted synthetic DMARDs (currently, Janus kinase inhibitors) should be added.
-
Biologic DMARDs or targeted synthetic DMARDs should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, interleukin-6 (IL-6) pathway inhibitors and targeted synthetic DMARDs may have some advantages compared with other biologic DMARDs.
-
If a biologic DMARD or targeted synthetic DMARD has failed, treatment with another biologic or targeted synthetic DMARD should be considered; if one tumor necrosis factor (TNF) inhibitor therapy has failed, patients may receive an agent with another mode of action or a second TNF inhibitor.
-
If a patient is in persistent remission after having tapered glucocorticoids, one can consider tapering biologic or targeted synthetic DMARDs, especially if this treatment is combined with a csDMARD.
-
If a patient is in persistent remission, tapering the csDMARD could be considered.
In its 2015 revised guidelines, the ACR included the following recommendations for treatment of patients with established RA [4] :
-
A treat-to-target stategy should be used regardless of disease activity. (Strong recommendation)
-
Low disease activity: DMARD monotherapy over TNF inhibitor; MTX is the preferred DMARD. (Strong recommendation)
-
Moderate or high disease activity: Combination DMARDs or add a TNF inhibitor, or non-TNF biologic or tofacitinib (Strong recommendation)
-
Moderate/high disease activity despite TNF inhibitor therapy: Switch to a non-TNF biologic with or without MTX over another TNF inhibitor or tofacitinib (Strong recommendation)
A change from 2012 to 2015 guidelines is that instead of switching from one anti-TNF biologic to another anti-TNF biologic because of continued activity, it is recommended to change first to a non-TNF biologic.
-
Juvenile rheumatoid arthritis. Ankylosis in the cervical spine at several levels due to long-standing juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).
-
Juvenile rheumatoid arthritis. Widespread osteopenia, carpal crowding (due to cartilage loss), and several erosions affecting the carpal bones and metacarpal heads in particular in a child with advanced juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).
-
Rheumatoid arthritis. Rheumatoid changes in the hand. Photograph by David Effron MD, FACEP.
-
Rheumatoid arthritis. Rheumatoid nodules at the elbow. Photograph by David Effron MD, FACEP.
-
Rheumatoid arthritis. Soft-tissue swelling and early erosions in the proximal interphalangeal joints in a patient with rheumatoid arthritis of the hands.
-
Rheumatoid arthritis. Subluxation in the metacarpophalangeal joints, with ulnar deviation, in a patient with rheumatoid arthritis of the hands.
-
Rheumatoid arthritis. Coronal, T1-weighted magnetic resonance imaging scan shows characteristic pannus and erosive changes in the wrist in a patient with active rheumatoid arthritis. Courtesy of J. Tehranzadeh, MD, University of California at Irvine.
-
Rheumatoid arthritis. Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.
-
Boutonniere deformity.
-
Rheumatoid arthritis. Anteroposterior radiograph of the knee shows uniform joint-space loss in the medial and lateral knee compartments without osteophytosis. A Baker cyst is seen medially (arrowhead).
-
Rheumatoid arthritis. Ultrasonography-guided synovial biopsy of the second metacarpophalangeal joint of the right hand in a patient with rheumatoid arthritis of the hands. The biopsy needle is seen as a straight echogenic line on the left side of the image in an oblique orientation.
-
Plain lateral radiograph of the normal cervical spine taken in extension shows measurement of anterior atlantodental interval (yellow line) and posterior atlantodental interval (red line).
-
Rheumatoid arthritis. Lateral flexion view of the cervical spine shows atlantoaxial subluxation.
-
Rheumatoid arthritis. Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.
-
Rheumatoid arthritis. T1-weighted sagittal magnetic resonance image of the cervical spine shows basilar invagination with cranial migration of an eroded odontoid peg. There is minimal pannus. The tip of the peg indents the medulla, and there is narrowing of the foramen magnum due to the presence of the peg. Inflammatory fusion of several cervical vertebral bodies is shown.
-
Sagittal T2-weighted magnetic resonance image of cervical spine in same patient as in previous image. Compromised foramen magnum is easily appreciated, and there is increased signal intensity within upper cord; this is consistent with compressive myelomalacia. Further narrowing of canal is seen at multiple levels.
-
Rheumatoid arthritis. Lateral radiograph of the same patient as in Images 4-5. Midcervical vertebral-body fusions are shown. The eroded peg is difficult to visualize, but inferior subluxation of the anterior arch of C1 is shown.
-
Lateral radiograph of a normal cervical spine shows the McGregor line. The odontoid tip should not protrude more than 4.5 mm above the line, which is drawn from the posterior edge of the hard palate to the most caudal point of the occiput.
-
Normal lateral magnified radiograph of the cervical spine shows the Ranawat method of detection of cranial settling. This method is used to measure the distance from the center of the pedicles (sclerotic ring) of C2 to a line drawn connecting the midpoints of the anterior and posterior arches of C1. (Normal values are 15 mm or greater for males and 13 mm or greater for females.)
-
Lateral radiograph of the cervical spine shows how the cervical height index (CHI) is calculated. The distance from the center of the sclerotic ring of C2 to the tip of the spinous process of C2 (dotted line) is measured. This is then divided into the distance from the center of the sclerotic ring of C2 to the midpoint of the inferior border of the body of C7. A CHI of less than 2 mm is a sensitive predictor of neurologic deficit.
-
X-ray shows total hip replacement, with prosthesis, in patient with osteoarthritis.
-
Rheumatoid arthritis. This gross photo shows destruction of the cartilage and erosion of the underlying bone with pannus from a patient with rheumatoid arthritis.
-
Rheumatoid arthritis. The hallmark of rheumatoid arthritis is a perivascular mononuclear cell infiltrate in the synovium (pictured here). The early stages are noted to have plasma cells as well, and syphilis needs to be part of the differential diagnosis.
-
Rheumatoid arthritis. The inflammation involved in rheumatoid arthritis can be intense. It is composed of mononuclear cells and can resemble a pseudosarcoma.
-
Rheumatoid arthritis. A 72-year-old man with long-standing rheumatoid arthritis developed blue-grayish discoloration of his skin. He had been on hydroxychloroquine for approximately 15 years. The diagnosis was hydroxychloroquine-related hyperpigmentation. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
-
Rheumatoid arthritis. A 64-year-old woman with rheumatoid arthritis has developed nodules on the dorsal and volar aspect of her fingers, as well as the posterior aspect of her heels. The diagnosis is rheumatoid nodules with methotrexate-induced accelerated nodulosis. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
-
Rheumatoid arthritis. A 64-year-old woman with rheumatoid arthritis has developed nodules on the dorsal and volar aspect of her fingers, as well as the posterior aspect of her heels. The diagnosis is rheumatoid nodules with methotrexate-induced accelerated nodulosis. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
Tables
Disease Activity |
Recommendations |
Early RA (< 6 months) |
|
(Notable change from 2012 to 2015 guidelines: The 2015 guidelines do not recommend initial combination DMARD therapy in early RA with moderate to high disease activity) |
|
Established RA (=6 month or meets 1987 ACR RA classification criteria) |
If disease activity remains moderate or high despite DMARD monotherapy, ACR guidelines recommend one of the following:
|
If disease activity remains moderate or high despite use of a single anti-TNF biologic:
|
|
If disease activity remains moderate or high despite use of one anti-TNF biologic and one non-TNF biologic:
|
|
(Notable change from 2012 to 2015 guidelines: Instead of switching from one anti-TNF biologic to another anti-TNF biologic because of continued activity, it is recommended to change first to a non-TNF biologic) |
|
|
|
Result of Initial/Repeat TST or IGRA |
Recommendation |
Positive |
|
Negative |
In patients with RA but without risk factors or clinical suspicion for TB
|
In patients with RA and immunosuppression plus LTBI risk factors
|
|
Active/latent TB |
|
ACR = American College of Rheumatology; IGRA = interferon gamma release assay; LBTI = latent tuberculosis infection; RA = rheumatoid arthritis; TB = tuberculosis; TST = tuberculin skin test. Source: Singh JA, Saag KG, et al2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care and Research https://read.qxmd.com/doi/10.1002/art.39480 (2015). [4] |
|
Tool Type |
Tool |
Low/Minimal Disease |
Moderate Disease |
High/Severe Disease |
Patient-driven composite |
PAS, PAS |
0.26–3.70 |
3.71 to < 8.0 |
8.00–10.00 |
PASII |
0.26–3.70 |
3.71 to < 8.0 |
8.00–10.00 |
|
Patient and provider composite |
RAPID-3 |
>1.0–2.0 |
>2.0–4.0 |
>4.0–10 |
Patient, provider, and laboratory composite |
CDAI |
2.8–10.0 |
>10.0–22.0 |
>22.0 |
DAS28 |
2.6 to < 3.2 |
3.2–5.1 |
>5.1 |
|
SDAI |
>3.3–11.0 |
>11.0 to 26 |
>26 |
|
PAS= Patient Activity Scale; RAPID-3 = Routine Assessment of Patient Index Data with 3 measures; CDAI = Clinical Disease Activity Index; DAS28 = 28-joint Disease Activity Score (with either erythrocyte sedimentation rate or C-reactive protein level); SDAI = Simplified Disease Activity Index |
||||
