Guideline sources The following summarized guidelines for the evaluation and management of rheumatoid arthritis (RA) are prepared by our editorial team based on guidelines from the American College of Rheumatology (ACR 2023; 2021; 2016; 2010), the Japan College of Rheumatology (JCR 2022), the European League Against Rheumatism (EULAR 2022), the Royal Dutch Society for Physiotherapy (KNGF 2021), the Royal College of Ophthalmologists (RCOphth 2020), and the American College of Radiology (ACR 2017). 1 2 3 4 5 6 7 8 9 10 11 12 13 13 13 14 15 Definition RA is a chronic, systemic inflammatory disorder of autoimmune origin, which most prominently affects the lining of synovial joints. 13 Epidemiology The pathogenesis of RA involves a complex interplay between genotype and environmental triggers. Twin studies implicate genetic factors in RA, and an association with the HLA-DRB1 locus has been established. Smoking and other forms of bronchial stress increase the risk of RA among https://web.pathway.md/diseases/recHrqZburvOp0UtZ 1/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway persons with certain susceptibility. Infectious agents (such as EBV, CMV, proteus species, and E. coli) have been associated with RA, possibly through a mechanism involving molecular mimicry. The onset of RA is also linked with adverse life events, an association that is postulated to occur via neuroimmunologic interactions. 15 Pathophysiology The prevalence of RA in the United States is estimated at 410-450 persons per 100,000 population. 14 Disease course Synovitis occurs when leukocytes infiltrate the synovial compartment, a process mediated by leukocyte migration and endothelial activation in synovial microvessels, which upregulates the expression of adhesion molecules and chemokines. Over time, chronic synovial inflammation leads to destruction of articular cartilage and bony erosions. 13 Prognosis and risk of recurrence RA is associated with progressive disability, premature death, and high socioeconomic costs. Approximately 75-80% of patients achieve remission and low disease activity with modern medical therapies. 13 Calculator ACR/EULAR diagnostic criteria f Guidelines 1. Screening and diagnosis Indications for testing: test for RA in patients who have at least one joint with definite clinical synovitis, in whom the synovitis is not better explained by another disease. 2. Diagnostic investigations Diagnostic imaging: Obtain radiography (often showing characteristic disease distribution and imaging findings) as initial imaging in patients with suspected RA. E Obtain ultrasound or MRI to complement radiography by showing synovitis and identifying additional erosions. E https://web.pathway.md/diseases/recHrqZburvOp0UtZ 2/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway Pretreatment evaluation: screen for HBV infection in all patients eligible for treatment with conventional synthetic, biological, or targeted synthetic DMARDs, immunosuppressants, or corticosteroids (according to dose and duration). B Show 3 more 3. Medical management Goals of treatment: As per EULAR 2022 guidelines, aim to reach a target of sustained remission or low disease activity. A As per ACR 2021 guidelines, prefer a treat-to-target approach over usual care in patients not previously treated with biologic or targeted synthetic DMARDs. B Show 2 more DMARD monotherapy, general principles: As per EULAR 2022 guidelines, initiate DMARDs as soon as the diagnosis of RA is made. A Show 2 more As per JCR 2022 guidelines, initiate methotrexate in patients with active RA. B Show 2 more DMARD monotherapy (low disease activity): consider initiating hydroxychloroquine over other conventional synthetic DMARDs in DMARD-na ve patients with low disease activity. C Show 2 more DMARD monotherapy (moderate-to-high disease activity): initiate methotrexate over hydroxychloroquine or sulfasalazine in DMARD-na ve patients with moderate-to-high disease activity. B Show 7 more DMARD monotherapy (mode of administration and dosing): consider administering oral methotrexate over subcutaneous methotrexate in patients initiating methotrexate. C Show 3 more Adding/switching DMARDs: As per EULAR 2022 guidelines, consider initiating other conventional synthetic DMARDs in the absence of poor prognostic factors if the treatment target is not achieved with the first conventional synthetic DMARD strategy. C Show 3 more As per JCR 2022 guidelines, consider adding a conventional synthetic DMARD to methotrexate in patients with an inadequate response to methotrexate. C Show 14 more As per ACR 2021 guidelines, consider adding a biologic or targeted synthetic DMARD over triple therapy (addition of sulfasalazine and hydroxychloroquine) in patients taking maximally tolerated doses of methotrexate not achieved target. C https://web.pathway.md/diseases/recHrqZburvOp0UtZ 3/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway Show 4 more Tapering/discontinuing DMARDs: As per EULAR 2022 guidelines, consider tapering DMARDs (biologic/targeted synthetic or conventional synthetic DMARDs) if the patient is in persistent remission after having corticosteroid discontinuiation. B As per JCR 2022 guidelines, consider tapering conventional synthetic DMARDs in patients in remission or having low disease activity with a biologic DMARD or a JAK inhibitor in combination with a conventional synthetic DMARD. C Show 4 more As per ACR 2021 guidelines, consider continuing all DMARDs at their current dose in patients achieved target for at least 6 months. C Show 4 more Corticosteroids: As per EULAR 2022 guidelines, consider initiating short-term corticosteroids when initiating or changing conventional synthetic DMARDs in different dose regimens and routes of administration, but taper and discontinue rapidly as clinically feasible. B As per JCR 2022 guidelines, consider initiating short-term concomitant corticosteroids with conventional synthetic DMARDs in patients with active early RA. C As per ACR 2021 guidelines: Avoid administering short-term (< 3 months) corticosteroids with the initiation of conventional synthetic DMARDs in DMARD-na ve patients with moderate-to-high disease activity. D Do not administer longer-term ( 3 months) corticosteroids with the initiation of conventional synthetic DMARDs in DMARD-na ve patients with moderate-to-high disease activity. D Denosumab: consider initiating add-on therapy with anti-RANKL antibody to DMARDs to inhibit progression of bone erosion in patients with active RA and bone erosion. B NSAIDs: consider offering NSAIDs for pain relief in patients with RA. C 4. Nonpharmacologic interventions Self-management programs: consider offering a standardized self-management program in patients with RA. C Physical therapy: As per ACR 2023 guidelines: Advise consistent exercising in patients with RA. B Consider advising consistent aerobic, B aquatic, B resistance, B and mind-body exercises. B Consider offering hand therapy exercises in patients with hand involvement. C As per KNGF 2021 guidelines, elicit a comprehensive history to assess the overall health status and the impact of the disease on the patient's life. Assess and document the patient's current disease activity (extent and severity of joint pain, swelling, and limited joint ROM), the presence https://web.pathway.md/diseases/recHrqZburvOp0UtZ 4/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway of structural joint damage and deformities, general exercise tolerance, and muscle function during physical examination, including examination of the cervical spine and the jaw joints. E Show 6 more Occupational therapy: consider offering comprehensive occupational therapy in patients with RA. C Show 2 more Splinting and orthoses: consider offering splinting, orthoses, and/or compression in patients with hand and/or wrist involvement and/or deformity. C Show 2 more Joint protection and energy conservation: consider offering joint protection techniques, C activity pacing, energy conservation, activity modification, and/or fatigue management in patients with RA. C Assistive devices: consider offering assistive devices, adaptive equipment, and environmental adaptations in patients with RA. C Dietary modifications: consider advising a Mediterranean-style diet in patients with RA. C Show 2 more Psychosocial interventions: consider offering CBT and/or mind-body approaches in patients with RA. C Alternative and complementary therapies: As per ACR 2023 guidelines: Consider offering the following therapies in patients with RA: acupuncture C massage therapy C thermal modalities. C Avoid offering the following therapies in patients with RA: electrotherapy D chiropractic therapy. D As per KNGF 2021 guidelines: Avoid offering the following therapies in patients with RA: low-level laser therapy electrostimulation (including transcutaneous electrical nerve stimulation) ultrasound massage thermotherapy medical taping dry needling. D Do not offer passive mobilization of joints and muscles in patients with RA. D https://web.pathway.md/diseases/recHrqZburvOp0UtZ 5/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway 5. Specific circumstances Elderly patients: use methotrexate with full safety consideration in elderly patients with poor prognostic factors. B Show 2 more Patients with renal impairment: adjust the doses of DMARDs with careful consideration for safety in patients with moderate or severe renal dysfunction. B Patients with heart failure: As per JCR 2022 guidelines, avoid using TNF inhibitors in patients with severe HF. D As per ACR 2021 guidelines: Consider adding a non-TNF inhibitor biologic DMARD or targeted synthetic DMARD in patients with NYHA class III or IV HF and an inadequate response to conventional synthetic DMARDs. C Consider switching to a non-TNF inhibitor biologic DMARD or targeted synthetic DMARD if HF develops in patients taking a TNF inhibitor. C Patients with NAFLD: consider initiating methotrexate over alternative DMARDs in DMARD-na ve patients with nonalcoholic fatty liver disease, normal liver enzymes and LFTs, no evidence of advanced liver fibrosis and moderate-to-high disease activity. C Patients with subcutaneous nodules: Consider initiating methotrexate over alternative DMARDs in patients with subcutaneous nodules and moderate-to-high disease activity. C Consider switching to a non-methotrexate DMARD in patients taking methotrexate with progressive subcutaneous nodules. C Patients with pulmonary disease: As per JCR 2022 guidelines, consider initiating DMARDs in patients with ILD with careful monitoring for acute exacerbation of ILD. C As per ACR 2021 guidelines, consider initiating methotrexate over alternative DMARDs for the treatment of inflammatory arthritis in patients with moderate-to-high disease activity and clinically diagnosed mild and stable airway or parenchymal lung disease or incidental disease detected on imaging. C Patients with previous serious infections: Consider adding a conventional rather than biologic or targeted synthetic DMARD in patients with a serious infection within the previous 12 months and moderate-to-high disease activity despite conventional synthetic DMARD monotherapy. C Consider adding/switching to DMARDs rather than initiating/escalating the dose of corticosteroids in patients with a serious infection within the previous 12 months and moderate-to-high disease activity. C Patients with non-tuberculous mycobacterial pulmonary disease: consider administering the lowest possible dose of corticosteroids (discontinue if possible) in patients with NTM lung disease. https://web.pathway.md/diseases/recHrqZburvOp0UtZ 6/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway C Show 2 more Patients with hepatitis B: As per JCR 2022 guidelines, treat HBsAg-positive patients with RA in collaboration with a hepatologist. Treat HBV-infected, HBsAg-negative patients according to the usual treatment strategy with regular monitoring for HBV infection. B As per ACR 2021 guidelines, initiate prophylactic antiviral therapy over frequent monitoring of viral load and liver enzymes alone in HBcAb-positive (regardless of HBsAg status) patients initiating rituximab. B Show 2 more Patients with hepatitis C: As per JCR 2022 guidelines, treat HCV-infected patients with RA according to the usual treatment strategy in collaboration with a hepatologist. B As per ACR 2016 guidelines: Consider using the same management strategy outlined as for patients without a history of hepatitis C in patients who are receiving, or have received, effective antiviral treatment. C Consider using DMARDs, rather than TNF inhibitors, in patients who have not received effective antiviral treatment. C Patients with HTLV-1 infection: consider administering DMARDs in HTLV-1-positive patients under careful monitoring of the disease course. C Patients with hypogammaglobulinemia: consider continuing rituximab over switching to a different biologic DMARD or targeted synthetic DMARD in patients at target with persistent hypogammaglobulinemia without infection. C Patients with malignancy: As per JCR 2022 guidelines, consider initiating biologic DMARDs in patients with malignancy or past history of malignancy with informed consent in collaboration with the attending physician treating the malignancy. C As per ACR 2021 guidelines, consider initiating rituximab over other DMARDs in patients with moderate-to-high disease activity and a history of lymphoproliferative disorder for which rituximab is an approved treatment. C As per ACR 2016 guidelines: Consider using the same management strategy outlined for patients without a history of solid organ malignancy in patients with RA and a history of solid organ malignancy. C Consider initiating DMARDs rather than biologics or tofacitinib in patients with melanoma or non-melanoma skin cancer. C 6. Patient education https://web.pathway.md/diseases/recHrqZburvOp0UtZ 7/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway General counseling: consider providing customized information and advice to support effective self-management and optimize health and well-being in patients with RA. Provide information about RA and its possible consequences, advise on the importance of exercise and a healthy lifestyle (including decreasing stress and fatigue and the way this lifestyle can be achieved and maintained), and discuss treatment options. C 7. Preventative measures Routine immunizations: As per ACR 2023 guidelines, consider offering high-dose or adjuvanted influenza vaccination, rather than regular-dose influenza vaccination, in 65 years old patients with rheumatic or musculoskeletal diseases and in 18-65 years old patients with rheumatic or musculoskeletal diseases on immunosuppressive medications. C Show 17 more As per JCR 2022 guidelines, consider offering influenza and pneumococcal vaccines, but not live vaccines, in patients with RA treated with corticosteroids or DMARDs. C Prophylaxis for Pneumocystis jirovecii pneumonia: consider administering prophylaxis against P. jirovecii pneumonia in patients initiating high-dose corticosteroids, especially in combination with immunosuppressants and depending on the risk-benefit ratio. C 8. Follow-up and surveillance Assessment of treatment response: monitor patients with active disease every 1-3 months. Adjust therapy if there is no improvement by at most 3 months after the initiation of treatment or the target has not been reached by 6 months. B Management of difficult-to-treat disease: discuss the possibility of misdiagnosis and/or the presence of a coexistent mimicking disease in patients with presumed difficult-to-treat RA. B Show 10 more Monitoring of hydroxychloroquine/chloroquine treatment: obtain annual monitoring for retinopathy in all patients receiving hydroxychloroquine for > 5 years or chloroquine for > 1 year. B Show 17 more Likelihood Ratios Pertinent positives The following findings increase the probability of rheumatoid arthritis in adults. 1 1 Finding LR+ Value Positive anti-citrullinated cyclic peptide antibodies 13.4 https://web.pathway.md/diseases/recHrqZburvOp0UtZ 8/10 6/24/23, 2:57 PM Rheumatoid arthritis Pathway Positive RF 4 Pertinent negatives The following findings decrease the probability of rheumatoid arthritis in adults. 1 1 Finding LR- Value Negative anti-citrullinated cyclic peptide antibodies 0.3 Negative RF 0.3 References 1. Yutaka Kawahito, Akio Morinobu, Yuko Kaneko et al. Drug Treatment Algorithm and Recommendations from the 2020 update of the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis-Secondary Publication. Mod Rheumatol. 2022 Mar 16;roac017. Open 2. Liana Fraenkel, Joan M Bathon, Bryant R England et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. 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