Curbside Consults - February 2016 Save

The following is a collection of cases presented to me by rheumatology colleagues. Each has a challenging therapeutic or safety issue. Answers are based on experience with references from literature and guidelines.

Case 1. A 61 female patient with rheumatoid arthritis is being treated with leflunomide (LEF) 20 mg daily. She was treated by her allergist with prednisone 40 mg TID for 4 months for hypersensitivity pneumonia. New symptoms prompted a pulmonary consultation and she was diagnosed with atypical tuberculosis (nontuberculous mycobacterial infection).  She is presently on triple therapy with ethambutol, isoniazid and rifampin. Question:   Would you stop leflunomide?  

Answer: I would stop the LEF. LEF is one of the few DMARDs wherein the package insert says you need to check for TB. The drug was developed in countries where risk of TB is higher and thus screening was an important part of their early trials. Although the mechanisms whereby LEF increases risk is unclear, LEF treated patients are at higher risk of TB and there are numerous reports to attest to this (http://buff.ly/21ogBfA). Although, the reactivation risk with LEF may not be as high as that seen with TNF inhibition, it should be viewed as an added risk. In the case of NTM infections, treatment never truly eradicates, hence return to a drug that may have contributed to the risk (TNFi, prednisone, LEF) should be discouraged. Future treatment options for her RA could include abatacept, rituximab, tofacitinib, sulfasalazine, anakinra, tocilizumab, tofacitinib, and gold. Prednisone should be avoided as well. 

Case 2. One of my patients is being treated for bladder cancer with intravesical BCG treatments.  He had to stop the Xeljanz that he was receiving for RA. He is now flaring terribly. I have restarted low dose prednisone, but he needs to be on something else. Do we know anything about how long a patient has to remain off immunosuppressives in order to give the BCG treatment a chance to work? I have checked numerous references, but none comes close to answering this question. Do you happen to have any experience with this scenario?

Answer: This issue is not uncommon and there are clear rules about what not to do and some good suggestions on how to treat. There are numerous cases of BCG therapy leading to reactivation of TB with TNF therapy. This is a known risk of TNF inhibition and thus all drugs that significantly increase TB risk cannot be given while the patient is receiving BCG therapy. There is a very low and almost no risk with the use of tofacitinib, and thus I would not have stop tofacitinib if the patient was doing well on it. The risk of BCG reactivation and/or TB with drugs like tofacitinib, abatacept, rituximab and tocilizumab is > 100 fold lower than with a TNF inhibitor. You must stop TNFi when using BCG - numerous reports of spread and death from TB.   It is safe to use MTX (but not LEF), and tofacitinib, abatacept, rituximab, anakinra and tocilizumab to manage his RA. Obviously, use the lowest doses and least number of drugs as possible to keep this risk very low. All of this advice weakens if the patient is incredibly immunosuppressed from cancer or other reasons, or if he had TB in the past or if he is on very high doses of steroids.

Case 3. A 62 year old RA patient DMARDs on MTX and certolizumab wants to know if it is safe to receive vaccines, which vaccines and when should they be given in relation to her biologic injections?

Answer:  All vaccines are safe to give while on MTX (and other DMARDs) alone – this includes inactive (influenza IM, hepatitis B, pneumococcal) vaccines and live virus vaccines (H. zoster, yellow fever, nasal influenza, BCG). There is no need to hold, suspend or alter the dosing of the DMARD or low dose steroid. 
Live virus vaccines should NOT be administered while on a TNF inhibitor or recombinant human biologic, according to guidelines put forth by the CDC, ACIP, ACR and the American Thoracic Society. Patients  who must receive a live virus vaccine need to be off their biologic for a minimum of 2 weeks (preferably 4 weeks) before receiving the live virus vaccine (e.g., Zostavax) and should wait 2 weeks before resuming or initiating biologic therapy. I would not advise withdrawing a patient from biologic therapy to give a live virus vaccine unless it is mandatory (e.g., foreign travel requiring yellow fever vaccination) and then only if the benefits of vaccine protection clearly outweighed the risk of RA flare. Instead, the prudent practitioner should wait until the right opportunity to administer needed or desired live virus vaccine, such as when there is an interruption in biologic use due to illnees, surgery, lapse in insurance coverage, etc.

If you have a challenging or interesting clinical case that you would like an expert opinion on please email the case vignette (diagnosis, duration, therapies, important findings) and clinical or therapeutic question to: info@rheumnow.com.