¹Definitions of disease activity are discussed in and and and were categorized as low, moderate or high
²Patients were categorized based on presence or absence of one or more of the following poor prognostic features: functional limitation (e.g., health assessment questionnaire (HAQ) score or similar valid tools); extra-articular disease (e.g., presence of rheumatoid nodules, RA vasculitis, Felty’s syndrome); positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies (–); bony erosions by radiograph ()
HCQ, Hydroxychloroquine; MTX, methotrexate; DMARD, Disease-Modifying Anti-Rheumatic Drug- includes hydroxychloroquine, leflunomide, methotrexate, minocycline and sulfasalazine; HAQ-DI, Health Assessment Questionnaire Disability Index; TNF, Tumor-necrosis Factor
For the level of evidence supporting each recommendation, please see .

* Reassess after 3 months and proceed escalating therapy if Moderate or High Disease Activity in all instances except after treatment with non-TNF biologic (rectangle D), where reassessment is recommended at 6-months due to a longer anticipated time for peak effect
¹Definitions of disease activity are discussed in and and and were categorized as low, moderate or high
²Features of poor prognosis included the presence of one or more of the following: functional limitation (e.g., health assessment questionnaire (HAQ) score or similar valid tools); extra-articular disease (e.g., presence of rheumatoid nodules, RA vasculitis, Felty’s syndrome); positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies (–); bony erosions by radiograph ()
³Combination DMARD therapy with two DMARDs, which is most commonly methotrexate-based with few exceptions (for example, methotrexate + hydroxychloroquine, methotrexate + leflunomide, methotrexate + sulfasalazine, sulfasalazine + hydroxychloroquine) and triple therapy (methotrexate + hydroxychloroquine + sulfasalazine).
⁴Leflunomide can be added in patients with low disease activity after 3–6 months of minocycline, hydroxychloroquine, methotrexate or sulfasalazine
⁵If after 3 months of intensified DMARD combination-therapy or after a second DMARD has failed, the option is to add or switch to an anti-TNF biologic.
⁶Reassessment after treatment with non-TNF biologic is recommended at 6-months due to anticipation that a longer time to peak effect is needed for non-TNF compared to anti-TNF biologics.
⁷Any adverse event was defined as per the U.S. FDA as any undesirable experience associated with the use of a medical product in a patient. Serious adverse events were defined per the U.S. FDA (see below); all other adverse events were considered non-serious adverse events. The FDA definition of serious adverse event includes death, life-threatening event, initial or prolonged hospitalization, disability, congenital anomaly or an adverse event requiring intervention to prevent permanent impairment or damage.
For the level of evidence supporting each recommendation, please see .
MTX, methotrexate; LEF, leflunomide; HCQ, Hydroxychloroquine; TNF, Tumor-necrosis factor
DMARD, Disease-Modifying Anti-Rheumatic Drug include hydroxychloroquine, leflunomide, methotrexate, minocycline and sulfasalazine (therapies are listed alphabetically; azathioprine and cyclosporine were considered but not included)
DMARD monotherapy refers to treatment in most instances with hydroxychloroquine, leflunomide, methotrexate or sulfasalazine; in few instances, where appropriate, minocycline may also be used
Anti-TNF biologics include adalimumab, certolizumab, etanercept, infliximab, golimumab
Non-TNF biologics include abatacept, rituximab or tocilizumab (therapies are listed alphabetically)

¹Anergy panel testing is not recommended
²IGRA is preferred if patient has a history of Bacillus-Calmette-Guérin (BCG) vaccination
³Risk factors for TB exposure are defined based on a publication from the US Centers for Disease Control and Prevention (CDC) as: close contacts of persons known or suspected to have active tuberculosis; foreign-born persons from areas that have a high incidence of active tuberculosis (e.g., Africa, Asia, Eastern Europe, Latin America, and Russia); persons who visit areas with a high prevalence of active tuberculosis, especially if visits are frequent or prolonged; residents and employees of congregate settings whose clients are at increased risk for active tuberculosis (e.g., correctional facilities, long-term care facilities, and homeless shelters); health-care workers who serve clients who are at increased risk for active tuberculosis; populations defined locally as having an increased incidence of latent M. tuberculosis infection or active tuberculosis, possibly including medically underserved, low-income populations, or persons who abuse drugs or alcohol; and infants, children, and adolescents exposed to adults who are at increased risk for latent M. tuberculosis infection or active tuberculosis. ()
⁴If patient is immunosuppressed and false negative results more likely, consider repeating screening test(s) with TST or IGRA.
⁵Chest radiograph may also be considered when clinically indicated in patients with risk factors, even with a negative repeat TST or IGRA.
⁶Obtain respiratory (e.g., sputum, bronchoalveolar lavage) or other samples as clinically appropriate for AFB smear and culture. Consider referral to TB specialist for further work-up and treatment.
⁷In a patient diagnosed with latent or active TB, consider referral to a specialist for the recommended treatment.
⁸Patients who test positive for TST or IGRA at baseline often remain positive for these tests even after successful treatment of TB. These patients need monitoring for clinical signs and symptoms of recurrent TB disease, since repeating tests will not allow help in diagnosis of recurrent TB.
The level of evidence supporting each recommendation for TB reactivation was “C”, except for initiation of biologics in patients being treated for latent TB infection (LTBI), where the Level of Evidence was “B”)
TST, Tuberculin Skin Test; IGRA, Interferon-gamma release assay; AFB, Acid fast bacilli