Canadian Rheumatology Association (CRA) recommendation for the pharmacological management of RA with traditional and biologic DMARD.
| Recommendations | Level | Strength | |
|---|---|---|---|
| General RA management strategies | |||
| 1. | The goal of treatment is remission and, when not possible, minimal disease activity (I) while controlling symptoms, halting damage, preventing disability, and improving quality of life (IV) | I, IV | A |
| 2. | The presence of the following poor prognostic features should be assessed at baseline and considered when making treatment decisions: RF positivity, anti-CCP positivity, functional limitation, high number of swollen and tender joints, early erosions, extraarticular features, high ESR or CRP | II | B |
| 3. | RA care providers should monitor disease activity as frequently as every 1 to 3 months in patients with active RA (I). Patients with well controlled disease and patients in remission can be monitored at longer intervals (IV) | I, IV | A |
| 4. | Traditional and biologic DMARD therapy should be adjusted every 3–6 months, as long as the goal has not been achieved | I, IV | B |
| 5. | Radiographs of the hands and feet are recommended as frequently as every 6–12 months in patients with recent-onset disease (II). Radiographs can be performed at longer intervals in patients with established disease (IV) | II, IV | B |
| 6. | A change in therapy should be considered in patients with radiographic progression despite adequate clinical response | IV | D |
| Treatment with glucocorticoids | |||
| 7. | Glucocorticoids (oral, intramuscular, or intraarticular) can be added to DMARD therapy as part of the initial treatment strategy of patients with RA (I), and may be an option for managing flares, as bridge therapy while waiting for DMARD to take effect, or for symptom control if no other options exist (IV). Glucocorticoids should be used in the lowest possible dose and tapered as rapidly as clinically feasible (IV) | I, IV | A/D |
| Treatment with MTX/DMARD | |||
| 8. | In patients with persistent synovitis, DMARD should be introduced as soon as possible | I | A |
| 9. | MTX is the preferred DMARD with respect to efficacy and safety and should be the first DMARD used in patients with RA unless contraindicated | I | A |
| 10. | A complete blood count (II), liver (I) and renal biochemistry (II), and a chest radiograph (II) should be ordered prior to initiating MTX therapy. Screening for hepatitis B and C should be considered (III), and HIV testing is recommended in high-risk patients (IV) | I–IV | B/D |
| 11. | Dosing of MTX should be individualized to the patient (IV). MTX should be started oral or parenteral and titrated to a usual maximum dose of 25 mg/week by rapid dose escalation. In patients with an inadequate response or intolerance to oral MTX, parenteral administration should be considered (I) | I, IV | A |
| 12. | Initial combination therapy with traditional DMARD should be considered, particularly in patients with poor prognostic features, moderate-high disease activity, and in patients with recent-onset disease. Combination therapy should also be considered in patients who have an inadequate response to monotherapy | I | B |
| 13. | When treating with combination therapy, MTX should be used as the anchor drug unless contraindicated. Combinations not including MTX can be considered on a case-by-case basis | I | A |
| 14. | Combination therapy with leflunomide and MTX should be used with caution as it is associated with higher toxicity (gastrointestinal and liver) (I) and has no added benefit relative to other DMARD combinations (IV) | I, IV | A |
| Treatment with biologics | |||
| 15. | In patients being considered for biologic therapy, an inadequate response to DMARD is defined as moderate to high disease activity despite treatment with at least 2 DMARD (including MTX unless contraindicated) in mono or combination therapy after 3 months at target dose | IV | D |
| 16. | Routine laboratory tests (complete blood count, liver and renal biochemistry) and screening for hepatitis B and C (and HIV in high-risk patients) are recommended prior to initiating all biologic therapy. Screening for latent tuberculosis is recommended prior to anti-TNF, abatacept, and tocilizumab. Baseline antinuclear antibody testing could be considered prior to starting anti-TNF | IV | D |
| 17. | MTX coprescription with biologics is recommended for improved efficacy | I | A |
| 18. | Anti-TNF therapy is recommended for treatment of patients with RA after an inadequate response to DMARD (I). In exceptional circumstances involving patients with DMARD contraindications or high disease activity and poor prognostic factors (particularly early disease), anti-TNF therapy may be an option after failure of DMARD monotherapy or in DMARD naive patients | I | A |
| 19. | Abatacept is recommended for the treatment of patients with RA after inadequate response to DMARD or anti-TNF therapy | I | A |
| 20. | Rituximab is recommended for the treatment of patients with RF-positive RA after an inadequate response to DMARD or anti-TNF therapy | I | A |
| 21. | Patients should not be expected to flare before they are retreated with rituximab (IV). Retreatment can occur as early as 6 months if the patient has had an initial response but has persistent synovitis (II) | II, IV | C |
| 22. | Tocilizumab is recommended for the treatment of patients with RA after inadequate response to DMARD or anti-TNF therapy | I | A |
| 23. | In patients who have failed treatment with 1 anti-TNF due to lack of efficacy or toxicity the following options are recommended: switch to another anti-TNF (I, II), switch to another biologic with a different mechanism of action (abatacept, rituximab, tocilizumab) (I), or add MTX (or other DMARD) if anti-TNF was used in monotherapy (II) | I, II | B |
| 24. | In patients who have failed treatment with 2 anti-TNF a switch to another biologic with a different mechanism of action (abatacept, rituximab, tocilizumab)) is recommended | II/IV | C |
| 25. | In the absence of data on therapeutic strategies after failure of abatacept, rituximab, or tocilizumab the following options can be considered: switch to any biologic not previously tried and failed, add or switch to a traditional DMARD not previously tried and failed, or enroll the patient in a clinical trial with a new agent | IV | D |
| 26. | If a patient achieves sustained remission after discontinuation of NSAID and glucocorticoids, a reduction in traditional and biologic DMARD can be attempted with caution as a shared decision between the patient and physician | IV | D |
RA: rheumatoid arthritis; DMARD: disease-modifying antirheumatic drug; anti-CCP: anti-cyclic citrullinated peptide antibody; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; HIV: human immunodeficiency virus; MTX: methotrexate; NSAID: nonsteroidal antiinflammatory drug; RF: rheumatoid factor.