Guidelines the engine cites
Every drug class in the code map and every "standard of care" criterion a navigator reads points at a sentence in a published guideline, reproduced here word for word with its evidence grade. Nothing on this page is a treatment decision; it is the reference the trial criteria cite.
EULAR recommendations for the management of systemic lupus erythematosus: 2023 update
Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis 2024;83:15-29. doi:10.1136/ard-2023-224762
Applies to: systemic lupus erythematosus, lupus nephritis. Recommendations reproduced verbatim from Table 1; levels of evidence and grades in parentheses are the paper's.
Overarching principles
- SLE requires multidisciplinary, individualised management with patient education and shared decision-making, taking into consideration the costs to patient and society.
- SLE disease activity should be assessed at each clinic visit (the frequency depending on physician's discretion), with evaluation of organ damage (at least annually), using validated instruments.
- Non-pharmacological interventions, including sun protection, smoking cessation, healthy, balanced diet, regular exercise and measures to promote bone health are important to improve long-term outcomes
- Pharmacological interventions are directed by patient characteristics, type and severity of organ involvement, treatment-related harms, comorbidities, risk for progressive organ damage, and patient preferences.
- Early SLE diagnosis (including serological assessment), regular screening for organ involvement (especially nephritis), prompt initiation of treatment aiming at remission (or low disease activity if remission is not possible) and strict adherence to treatment are essential to prevent flares and organ damage, improve prognosis and enhance quality of life.
Recommendations
- Hydroxychloroquine is recommended for all patients (1b/A), unless contraindicated, at a target dose of 5 mg/kg real body weight/day (2b/B) but individualised based on risk for flare (2b/B) and retinal toxicity.
- Glucocorticoids, if needed, are dosed based on the type and severity of organ involvement (2b/C), and should be reduced to maintenance dose of ≤5 mg/day (prednisone equivalent) (2a/B) and, when possible, withdrawn; in patients with moderate-to-severe disease, pulses of intravenous methylprednisolone (125–1000 mg/day, for 1–3 days) (3b/C) can be considered.
- In patients not responding to hydroxychloroquine (alone or in combination with glucocorticoids) or patients unable to reduce glucocorticoids below doses acceptable for chronic use, addition of immunomodulating/immunosuppressive agents (eg, methotrexate (1b/B), azathioprine (2b/C) or mycophenolate (2a/B)) and/or biological agents (eg, belimumab (1a/A) or anifrolumab (1a/A)) should be considered.
- In patients with organ-threatening or life-threatening disease, intravenous cyclophosphamide (2b/C) should be considered; in refractory cases, rituximab (2b/C) may be considered.
- Treatment of active skin disease should include topical agents (glucocorticoids, calcineurin inhibitors) (2b/B), antimalarials (hydroxychloroquine, chloroquine) (1a/A), and/or systemic glucocorticoids (4/C) as needed, with methotrexate (1b/B), mycophenolate (4/C), anifrolumab (1a/A), or belimumab (1a/B) considered as second-line therapy.
- In active neuropsychiatric disease attributed to SLE, glucocorticoids and immunosuppressive agents for inflammatory manifestations (1b/A) and antiplatelet agents/anticoagulants for atherothrombotic/aPL-related manifestations (2b/C) should be considered.
- For acute treatment of severe autoimmune thrombocytopenia, high-dose glucocorticoids (including pulses of intravenous methylprednisolone) (4/C), with or without intravenous immunoglobulin G (4/C), and/or rituximab (2b/B), and/or high-dose intravenous cyclophosphamide (4/C), followed by maintenance therapy with rituximab (2b/B), azathioprine (2b/C), mycophenolate (2b/C), or cyclosporine (4/C) should be considered.
- Patients with active proliferative lupus nephritis should receive low-dose (EuroLupus) intravenous cyclophosphamide (1a/A) or mycophenolate (1a/A) and glucocorticoids (pulses of intravenous methylprednisolone followed by lower oral doses); combination therapy with belimumab (either with cyclophosphamide or mycophenolate (1b/A)) or calcineurin inhibitors (especially voclosporin or tacrolimus, combined with mycophenolate, 1b/A) should be considered.
- Following renal response, treatment of lupus nephritis should continue for at least 3 years (2b/B); patients initially treated with mycophenolate alone or in combination with belimumab or a calcineurin inhibitor should remain on these drugs (1a/A), whereas azathioprine or mycophenolate should replace cyclophosphamide for those initially treated with cyclophosphamide alone (1a/A) or in combination with belimumab (1a/A).
- In patients at high-risk for renal failure (defined as reduced GFR, histological presence of cellular crescents or fibrinoid necrosis, or severe interstitial inflammation), high-dose (NIH regimen) intravenous cyclophosphamide (1a/A) in combination with pulse intravenous methylprednisolone, can be considered.
- In patients with SLE achieving sustained remission, gradual tapering of treatment should be considered, with withdrawal of glucocorticoids first (2a/B).
- SLE associated with thrombotic antiphospholipid syndrome (APS) should be managed with long-term vitamin K antagonists after the first arterial or unprovoked venous thrombotic event (1b/B); low dose aspirin (75–100 mg/day) should be considered in patients with SLE without APS but with high-risk aPL profile (2a/B).
- Immunisations for the prevention of infections (herpes zoster virus, human papillomavirus, influenza, COVID-19 and pneumococcus), management of bone health, nephroprotection and cardiovascular risk, and screening for malignancies, should be performed (5/D).
What the code map takes from it
| Class | Agent | From |
|---|
| standard of care | hydroxychloroquine | 1 |
| standard of care | methotrexate | 3 |
| standard of care | azathioprine | 3 |
| standard of care | mycophenolate | 3 |
| standard of care | leflunomide | 3 |
| standard of care | cyclophosphamide | 8 |
| add-on | belimumab | 8 |
| add-on | anifrolumab | 3 |
| add-on | voclosporin | 8 |
| add-on | tacrolimus | 8 |
| add-on | cyclosporine | 7 |
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update
Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3-18. doi:10.1136/ard-2022-223356
Applies to: rheumatoid arthritis. Recommendations reproduced verbatim from Table 1; levels of evidence and grades in parentheses are the paper's.
Overarching principles
- Treatment of patients with RA should aim at the best care and must be based on a shared decision between the patient and the rheumatologist.
- Treatment decisions are based on disease activity, safety issues and other patient factors, such as comorbidities and progression of structural damage.
- Rheumatologists are the specialists who should primarily care for patients with RA.
- Patients require access to multiple drugs with different modes of action to address the heterogeneity of RA; they may require multiple successive therapies throughout life.
- RA incurs high individual, medical and societal costs, all of which should be considered in its management by the treating rheumatologist.
Recommendations
- Therapy with DMARDs should be started as soon as the diagnosis of RA is made. (1a / A)
- Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient. (1a / A)
- Monitoring should be frequent in active disease (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. (2b / B)
- MTX should be part of the first treatment strategy. (1a / A)
- In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the (first) treatment strategy. (1a / A)
- Short-term glucocorticoids should be considered when initiating or changing csDMARDs, in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible. (1a / A)
- If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors, other csDMARDs should be considered. (5 / D)
- If the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present, a bDMARD should be added; JAK-inhibitors may be considered, but pertinent risk factors* must be taken into account. (Efficacy: 1a; Safety: 1b / Efficacy: A; Safety: B)
- bDMARDs and tsDMARDs* should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, IL-6 pathway inhibitors and tsDMARDs* may have some advantages compared with other bDMARDs. (Efficacy: 1a / Efficacy: A)
- If a bDMARD or tsDMARD* has failed, treatment with another bDMARD or a tsDMARD* + should be considered; if one TNF or IL-6 receptor inhibitor therapy has failed, patients may receive an agent with another mode of action or a second TNF-/ IL-6R-inhibitor++. (Efficacy: 1a/+5/++3; safety: 1b / Efficacy: A/+D; Safety: B; IL-6R-inhibition: C)
- After glucocorticoids have been discontinued and a patient is in sustained remission, dose reduction of DMARDs (bDMARDs/tsDMARDs* and/or csDMARDs) may be considered. (1b / A)
*The following risk factors for cardiovascular events and malignancies must be considered when intending to prescribe a JAK-inhibitor: Age over 65 years, history of current or past smoking, other cardiovascular risk factors (such as diabetes, obesity, hypertension), other risk factors for malignancy (current or previous history of malignancy other than successfully treated non-melanoma skin cancer), risk factors for thromboembolic events (history of myocardial infarction or heart failure, cancer, inherited blood clotting disorders or a history of blood clots, as well as patients taking combined hormonal contraceptives or hormone replacement therapy, undergoing major surgery or immobile).
Glossary rows the engine reads (Table 1)
| Term | Definition |
|---|
| Low dose glucocorticoids | < 7.5 mg/day prednisone equivalent |
| Short-term | Up to 3 months |
| Conventional synthetic DMARDs | For example, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine |
| Targeted synthetic DMARDs | For example, baricitinib, filgotinib, tofacitinib, upadacitinib |
| Biological originator DMARDs | TNFi: adalimumab, certolizumab, etanercept, golimumab, infliximab; IL-6Ri: sarilumab, tocilizumab; Co-stimulation-i: abatacept; anti-B-cell (CD20): rituximab |
| Biosimilar DMARDs | Currently for adalimumab, etanercept, infliximab, rituximab |
What the code map takes from it
| Class | Agent | From |
|---|
| csDMARD | methotrexate | 4 |
| csDMARD | leflunomide | 5 |
| csDMARD | sulfasalazine | 5 |
| csDMARD | hydroxychloroquine | Table 1 |
| tsDMARD | baricitinib | Table 1 |
| tsDMARD | filgotinib | Table 1 |
| tsDMARD | tofacitinib | Table 1 |
| tsDMARD | upadacitinib | Table 1 |
| bDMARD | adalimumab | Table 1 |
| bDMARD | certolizumab | Table 1 |
| bDMARD | etanercept | Table 1 |
| bDMARD | golimumab | Table 1 |
| bDMARD | infliximab | Table 1 |
| bDMARD | sarilumab | Table 1 |
| bDMARD | tocilizumab | Table 1 |
| bDMARD | abatacept | Table 1 |
| bDMARD | rituximab | Table 1 |
Protocol criteria derived from these
| Protocol | Criterion | Derived from |
|---|
| AMYN-SLE-001 | on_standard_tx | EULAR 2023 SLE, recommendations 1, 3 and 8 |
| AMYN-RA-004 | on_standard_tx | EULAR 2022 RA, recommendations 4 and 5 and Table 1 |
Not yet in the product
Diseases the engine encodes whose guideline is not reproduced here yet, and the paper that would fill the slot.
| Disease | Guideline |
|---|
| crohn's disease | Torres J, et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis 2020;14:4-22. doi:10.1093/ecco-jcc/jjz180 |
| ulcerative colitis | Raine T, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis 2022;16:2-17. doi:10.1093/ecco-jcc/jjab178 |
| plaque psoriasis | Nast A, et al. EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris. J Eur Acad Dermatol Venereol 2020;34:2461-2498. doi:10.1111/jdv.16915 |
| asthma | Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2024 report. |
Generated by demo/build_guidelines.py from amyn/data/guidelines. Each paper's licence terms apply to the quoted text; the articles themselves are not redistributed.