EULAR: Screen for TB, other infections in patients starting DMARDs
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Patients with autoimmune inflammatory rheumatic diseases should be screened for tuberculosis, hepatitis B and other infections before starting disease-modifying antirheumatic drugs, according to new guidelines published by EULAR.
“Opportunistic and chronic infections, that is, those which present more commonly or more severely in people who are immunocompromised, are encountered in the setting of autoimmune inflammatory rheumatic diseases (AIIRD) and are often associated with immunosuppressive and immunomodulatory treatments used for these diseases,” George E. Fragoulis, MD, PhD, of the National and Kapodistrian University of Athens, in Greece, and colleagues wrote in the Annals of the Rheumatic Diseases.
“Setting a single set of guidelines for infection screening and prophylaxis is challenging, as recommendations and procedures cannot be unified across all infections and organisms due to differences in area of residence, type of AIIRD and associated risk, the antirheumatic treatment received, and other factors that may present additional layers of complexity, such as age and comorbidities,” they added.
To establish a new set of overarching principles and recommendations for the screening and prophylaxis of chronic infections in patients with AIIRD, EULAR established a task force that included rheumatologists, epidemiologists, patient researchers, infectious disease physicians and pulmonologists. A literature review included papers published through Dec. 5, 2021, while those published after this date, but before the second task force meeting, were also considered. The results of the review were presented at the second virtual task force meeting, which took place in several parts throughout December 2021 and January 2022.
Recommendations and overarching principles were included if they reached a consensus of 75% or greater during the first round of voting. In the second round, a minimum consensus of 67% was required, while a threshold of 50% was used in the third round.
The task force ultimately established four overarching principles and eight recommendations.
The overarching principles state that, in patients with AIIRD, the risk for chronic or opportunistic infections should be discussed before beginning DMARDs or other immunosuppressant therapies. Additionally, they stress the importance of cross-specialty collaboration, and argue that individual risk factors should play into the decision to screen. Lastly, they state that physicians should consider national guidelines and recommendations, as well as regional factors, in appropriate patients.
The eight approved EULAR recommendations are:
- Screening for latent tuberculosis is recommended prior to starting traditional synthetic or biologic DMARDs. Additionally, screening should be considered in patients at risk for latent tuberculosis before beginning other immunosuppressive therapies.
- Latent tuberculosis screenings should follow national or international guidelines.
- Therapy for latent tuberculosis should follow national and international guidelines.
- Patients being considered for DMARDs or other immunosuppressant therapies should be tested for hepatitis B.
- Before starting DMARDs or other immunosuppressive therapies, patients should be screened for chronic hepatitis C.
- Patients beginning biologic DMARDs should be screened for HIV. Screening is also recommended for patients initiating other DMARDs or immunosuppressive therapies.
- Patients starting DMARDs or other immunosuppressive therapies who are not immune to varicella zoster virus should be told about pre-exposure prophylaxis following contact with the disease.
- Prophylaxis against Pneumocystis jirovecii pneumonia should be considered in patients who will receive large doses of glucocorticoids.
“This is the first set of EULAR recommendations addressing the need for guidance about screening and prophylaxis in people living with AIIRD,” Fragoulis and colleagues wrote. “Variations relating to treatment, geographical and other differences were taken into account.”
References:
- Hsu HC, et al. Clin Rheumatol 2021;doi:10.1007/s10067-021-05660-4.
- Mecoli CA, et al. Curr Rheumatol Rep 2020;doi:10.1007/s11926-020-0883-0.
- Mori S, et al. Clin Med Insights Circ Respir Pulm Med 2015;doi:10.4137/CCRPM.S23286.
- Winthrop KL, et al. Ann Rheum Dis 2015;doi:10.1136/annrheumdis-2015-207841.
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
The EULAR recommendations noted in the above publication are in some ways different from what many of us are doing in practice. They recommend screening for latent tuberculosis not only in patients prior to receiving biologics (bDMARDs) or targeted synthetics (tsDMARDs), but also for patients at increased risk for latent TB prior to conventionally synthetics (csDMARDs), immunosuppressives, and/or glucocorticoids. I don’t know how many rheumatologists screen for latent TB in patients receiving methotrexate, leflunomide, azathioprine, prednisone, etc. I generally do not screen these patients.
For prednisone, they recommend screening patients receiving greater than 15 mg per day for more than 4 weeks. They consider increased risk for TB to be alcohol abuse, smoking, living with someone with TB, or living in a country endemic for TB. For screening, they recommend an interferon-gamma release assay (IGRA) over the tuberculin skin test (TST). I think many of us have gone to IGRA over the TST. It is easier for the patient and the clinic, and the results are usually “black and white,” with the laboratory result providing documentation for precertification of therapy.
EULAR also recommends a chest X-ray be completed for screening as a “negative IGRA or TST cannot exclude active TB or rule out latent TB.” I haven’t been doing screening chest X-rays and wonder how many rheumatologists are doing this. We usually do this after the patient has a positive IGRA.
The EULAR guidelines also recommend screening for hepatitis B virus (HBV) infection in all patients considered for csDMARDs, bDMARDs, tsDMARDs, immunosuppressants and glucocorticoids (dose and duration as above). I have not been screening for HBV in patients on csDMARDs, immunosuppressants or glucocorticoids. In the United States, an estimated 875,000 persons are living with chronic HBV (+HBsAg), although prior or resolved HBV (+HBcAb and −HBsAg) is much more common, affecting up to 11 million persons. Up to 75% of patients with chronic HBV are unaware of their status.
Screening for HBV should include HBsAg, HBcAb (total), and HBsAb. HBsAg positivity is a hallmark of acute or chronic HBV, the latter characterized by persistence of HBsAg for more than 6 months. HBcAb (total) detects IgG and IgM antibodies to an intracellular viral antigen. This antibody response develops after natural infection and can identify patients with prior or resolved HBV, and is positive in chronic HBV but will be negative in vaccinated individuals.
HBsAb detects antibodies to HBsAg that develop either after natural infection or vaccination. It confers lifelong immunity in most immunocompetent individuals. In immunocompromised individuals with prior or resolved HBV, the presence of HBsAb does not preclude HBV reactivation. The tests for HBV that are not indicated for screening are HBV DNA, HBcAb IgM, HBeAg, and HBeAb. The ACR Guidelines from 2021 strongly recommend prophylactic antiviral therapy “over frequent monitoring alone for patients initiating rituximab who are hepatitis B core antibody positive (regardless of hepatitis B surface antigen status).”
They also strongly recommend prophylactic antiviral therapy “over frequent monitoring alone for patients initiating any bDMARD or tsDMARD who are hepatitis B core antibody positive and hepatitis B surface antigen positive.”
Finally, conditionally recommend frequent monitoring alone “over prophylactic antiviral therapy for patients initiating a bDMARD other than rituximab or a tsDMARD who are hepatitis B core antibody positive and hepatitis B surface antigen negative.” Other EULAR recommendations regarding screening for HIV, post-exposure prophylaxis for varicella virus exposure, and prophylaxis for PCP are of interest and need to be considered.
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