- Focus on common clinical scenarios, not exceptional cases
- Cost is a consideration in these recommendations. However, explicit cost-effectiveness analyses were not conducted.
- Disease activity measurement using an ACR-recommended measure should be performed in a majority of encounters with patients with rheumatoid arthritis (RA).1
- Functional status assessment using a standardized, validated measure should be performed routinely for RA patients, at least once per year, but more frequently if disease is active. Examples of commonly used functional status measures include Health Assessment Questionnaire (HAQ), Health Assessment Questionnaire-II (HAQ-II), Multidimensional Health Assessment Questionnaire (MD-HAQ), Patient-Reported Outcomes Measurement Information System , Physical Function 10-item, PROMIS Physical Function 20-item, and PROMIS Physical Function Computerized Adaptive Tests (PROPFCAT).
- If a patient has low RA disease activity or is in clinical remission, switching from one therapy to another should be considered only at the discretion of the treating physician in consultation with the patient.
Arbitrary switching between RA therapies based only on a payer/insurance company policy is not recommended.
- A treatment recommendation favoring one medication over another means that the preferred medication would be the recommended first option. However, favoring one medication over the other does not imply that the non-favored medication is contraindicated for use in that situation; it may still be a potential option under certain conditions.
Table 1. Definitions
Key Terms and Definitions
- Adult RA patient
- Adults, 18 years and older, meeting the ACR RA classification criteria.2, 3
- Health Benefits and Harms
- Efficacy and safety of treatments including desirable and undesirable effects.
- Early RA
- RA with duration of disease/symptoms of <6 months, where “duration” denotes the length of time the patient has had symptoms/disease, not the length of time since RA diagnosis.
- Established RA
- RA with duration of disease/symptoms of ≥6 months OR meeting 1987 ACR RA classification criteria.a
- Disease activity
- Categorized as low, moderate, or high as per validated scales
(Table 3). Moderate and high disease activity categories were combined, as used previously for the 2012 ACR RA treatment recommendations.1
- RA remission
- A joint ACR-EULAR task force defined remission as a tender joint count, swollen joint count, C-reactive protein (mg/dL) and patient global assessment ≤1 each or a Simplified Disease Activity Score (DAS) of ≤ 3.3,4 one of 6 ACR-endorsed disease activity measures.b
- Optimal dosing of RA treatments
- Dosing to achieve a therapeutic target derived from mutual patient-clinician consideration of patient priorities, and
- Given for ≥3 months before therapy escalation or switching.
- DMARD failure
- Failure of traditional/conventional DMARD(s) due to lack of efficacy/desired response or side effects.
- Biologic failure
- Failure of biologic(s) due to lack of efficacy/desired response or side effects.
- Secondary biologic failure
- A biologic was efficacious initially but subsequently became inefficacious.
- Active hepatitis B infection
- Hepatitis B surface antigen positive, Hepatitis B surface antibody negative, Hepatitis B core antibody total positive (less important), AST/ALT typically increased, HBV DNA positive (if checked).
- Hepatitis C infection
- HCV antibody positive, HCV RNA positive, AST/ALT typically increased.
- NYHA class III and IV
- NYHA class III includes patients with cardiac disease resulting in marked limitation of physical activity with less than ordinary physical activity causing fatigue, palpitation, dyspnea, or angina, but no symptoms at rest.
- NYHA class IV includes patients with cardiac disease resulting in inability to carry on any physical activity without discomfort, symptoms of heart failure are present even at rest, and discomfort increases if any physical activity is undertaken.5
NOTE: All numeric superscripts refer to Source References on page 17. Alphabetic superscripts refer to footnotes at the end of figures and tables.
a New classification criteria for RA (ACR /EULAR collaborative initiative) were published in 2010.3 The definition of established RA is based on the 1987 ACR RA Classification criteria,2 since the 2010 ACR RA classification allows a much earlier diagnosis.
b Any of the ACR-recommended disease activity measures may be chosen, as described in Anderson
Table 2. Agents Used in Treating RA
Drug Category and Definitions
- Methotrexate (MTX)
- A disease modifying antirheumatic drug (DMARD)
Used either oral or subcutaneous
- Traditional/conventional DMARDs including hydroxychloroquine (HCQ), leflunomide (LEF), methotrexate or sulfasalazine (SSZ) (excludes azathioprine,
cyclosporine, minocycline and goldb). It does not include tofacitinib,
which is considered separately.
- DMARD monotherapy
- Most often defined as the use of MTX monotherapy, but may also be SSZ, HCQ, or LEF
- Double DMARD therapy
- MTX SSZ, MTX HCQ, SSZ HCQ, or combinations with LEF
- Triple DMARD therapy
- MTX SSZ HCQ
- DMARD combination therapy
- Double or triple traditional/conventional DMARD therapy
- Oral synthetic small molecule
- TNFi biologic or non-TNF biologic (excludes anakinraa)
- Low dose glucocorticoid
- ≤10 mg/day of prednisone (or equivalent).
- High dose glucocorticoid
- >10 mg/day of prednisone (or equivalent) and ≤60 mg/day with a rapid taper
(e.g., COBRA regimen6)c
- Short-term glucocorticoid
- <3 month treatment
a Anakinra was considered but not included in these guidelines due to its infrequent use in RA and lack of new data since 2012.
b Azathioprine, cyclosporine, minocycline and gold were considered but not included in these guidelines due to their infrequent use in RA and/or lack of new data since 2012.
c Regimen based on that described in the Combinatietherapie Bij Ruematoide Artritis (COBRA).5
Table 3. Instruments to Measure Rheumatoid Arthritis Disease Activity and to Define Remissiona
|Patient Activity Scale (PAS) or PASII7||Remission: 0–0.25|
Low activity: >0.25–3.7
Moderate activity: >3.7–<8.0
High activity: ≥8.0
|Routine Assessment of Patient Index Data 3 (RAPID3)8||Remission: 0–1.0|
Low activity: >1.0–2.0
Moderate activity: >2.0–4.0
High activity: >4.0–10
|Clinical Disease Activity Index (CDAI)9||Remission: ≤2.8|
Low activity: >2.8–10.0
Moderate activity: >10.0–22.0
High activity: >22
|Disease Activity Score (DAS) 28|
erythrocyte sedimentation rate (ESR)10, b
Low activity: ≥2.6–<3.2
Moderate activity: ≥3.2–≤5.1
High activity: >5.1
|Simplified Disease Activity Index (SDAI)11||Remission: ≤3.3|
Low activity: >3.3–≤11.0
Moderate activity: >11.0–≤26
High activity: >26
a These six measures were endorsed by the ACR in 2012. Other measures are now available to clinicians, but they were not included in this guideline because it was beyond the scope of this review.
b Adapted from Anderson J et al.1