The 2012 updates address:
- the indications for starting or switching DMARDs and biologic drugs
- the use of biologics in high-risk patients, including those with hepatitis, congestive heart failure, and malignancy
- tuberculosis screening for patients starting or currently taking biologic drugs
- vaccination in patients starting or currently taking DMARDs or biologic drugs
The recommendations were based on literature searches of PubMed and the Cochrane Database of Systematic Reviews, clinical scenario testing, and expert opinion. The literature was searched for 8 DMARDs: azathioprine (Imuran), cyclosporine, hydroxychloroquine (Plaquenil), leflunomide (Arava), methotrexate, minocycline (Minocin), gold, and sulfasalazine (Azulfidine) -- and 9 biologic drugs: abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), and tocilizumab (Actemra). Due to infrequent use of the drugs and the lack of new data derived from the searches, azathioprine, cyclosporine, gold, and anakinra were not included in the recommendations. Orencia, Rituxan, Kineret, and Actemra are non-TNF biologic drugs. Enbrel, Remicade, Humira, Simponi, and Cimzia are TNF blockers.
For patients with early rheumatoid arthritis (defined as having rheumatoid arthritis for less than 6 months) and patients with established rheumatoid arthritis being treated with any DMARD or biologic drug, the goal of treatment is low disease activity or remission.
Starting or Switching DMARDs and Biologic Drugs
- DMARD monotherapy (treatment with a single drug) was recommended for early rheumatoid arthritis patients with low disease activity or with moderate/high disease activity in the absence of poor prognostic features (i.e. poor predicted course of the disease).
- DMARD combination therapy was recommended for early rheumatoid arthritis patients with moderate or high disease activity and poor prognostic features.
- The use of a TNF blocker with or without methotrexate was recommended for early rheumatoid arthritis patients with high disease activity and poor prognostic features. If the TNF blocker is infliximab (Remicade), however, it should be used with methotrexate.
- For patients with established rheumatoid arthritis, if after 3 months of DMARD monotherapy the patient declines from low disease activity to moderate or high disease activity, methotrexate, hydroxychloroquine, or leflunomide (Arava) should be added.
- After 3 months of methotrexate or methotrexate/DMARD combination therapy, add another non-methotrexate DMARD or switch to another non-methotrexate DMARD if the established patient still has moderate to high disease activity -- or add or switch to a TNF blocker, abatacept (Orencia), or rituximab (Rituxan).
- After 3 months of treatment with a TNF blocker, if the patient has moderate/high disease activity related to lack of response or loss of benefit from the treatment, switching to another TNF blocker or a non-TNF biologic is recommended.
- If there is moderate/high disease activity after 6 months of treatment with a non-TNF biologic due to lack of response or loss of benefit, the patient should be switched to a different non-TNF biologic or to a TNF blocker.
- If the patient has high disease activity and fails a TNF blocker due to a serious adverse event, switching to a non-TNF biologic is recommended.
- If the patient has moderate/high disease activity and fails a TNF blocker due to a non-serious adverse event, switching to another TNF blocker or a non-TNF biologic is recommended.
- If the patient has moderate/high disease activity after failing a non-TNF biologic due to an adverse event, switching to another non-TNF blocker or a TNF blocker is recommended.
Use of Biologics in Rheumatoid Arthritis Patients With Hepatitis, Malignancy, or Congestive Heart Failure
- Etanercept (Enbrel) is recommended for rheumatoid arthritis patients with hepatitis C.
- Biologic drugs are not recommended for rheumatoid arthritis patients with untreated chronic hepatitis B or certain treated chronic hepatitis B patients.
- Starting or resuming biologic treatment is recommended for patients treated for solid malignancies longer than 5 years ago or for patients who have been treated for nonmelanoma skin cancer longer than 5 years ago.
- TNF blockers are not recommended for rheumatoid arthritis patients with moderate or severe congestive heart failure.
Tuberculosis (TB) Screening
- Screening for latent TB infection is recommended for rheumatoid arthritis patients considering biologic treatment.
- Irrespective of risk factors for latent TB infection, the tuberculin skin test or interferon-gamma-release-assay should be performed on patients who are ready to start biologic treatment.
Vaccinations for Patients Starting or Receiving DMARDs or Biologic Drugs
- Killed vaccines (pneumococcal, influenza, and hepatitis B), recombinant (human papillomavirus), and live attenuated (herpes zoster) vaccines should be given before starting a DMARD or biologic drug.
- If not already done, the killed or recombinant vaccines should be given to patients already taking a DMARD or biologic drug.
- The herpes zoster vaccine can be given to those already taking a DMARD.
The Bottom Line
The updated information clarifies recommendations for most common cases of rheumatoid arthritis. The recommendations apply to most but not all rheumatoid arthritis patients. There will be exceptions.
Update of the 2008 ACR Recommendations for Use of DMARDs and Biologics in the Treatment of Rheumatoid Arthritis. Arthritis Care & Research. pp. 625-639. Singh JA et al. May 2012.