Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register
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  • Published on:
    Response to: ‘Correspondence on 'Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register.' by Huang et al.
    • Anja Strangfeld, PD Dr Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
    • Other Contributors:
      • Imke Redeker, Dr

    We thank Huang and co-authors (1) for their correspondence on our work (2). We want to take the opportunity to clarify the raised issues.
    The first issue raised was the question regarding the investigation of dose-dependent effects of treatments. For treatments in which dose-dependent effects are important, different doses have been studied and the relationship has been shown. This is the case with the use of glucocorticoids (GC). Using an Andersen-Gill model with inverse probability weights we found an adjusted Hazard ratio (HR) for herpes zoster (HZ) of 4.42 (2.50 to 7.83) for GC of more than 10 mg/day compared to no GC and 1.47 (1.17 to 1.85) for GCs of 5 to 10 mg/day. To answer the question about a possible effect of (different) duration of exposure on the outcome we would like to point out, that this information (exposure duration of disease-modifying anti-rheumatic drugs (DMARDs)) is naturally accommodated in the Andersen-Gill model which we used to calculate estimates.
    Regarding the second issue raised, the analysis of other immunosuppressant treatments, we admit that we did not consider those treatments in our analyses due to the rare prescribing rates of these medications, except from leflunomide, especially in monotherapy. In particular, the proportion of patients with concomitant use of leflunomide with biologic DMARDs was approximately 10%, while concomitant use of cyclosporin with biologic DMARDs was below 1% and only 4 patients received mycophenol...

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    Conflict of Interest:
    None declared.
  • Published on:
    Correspondence on ‘ Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register. ’
    • Yi-Hsiang Huang, medical student School of Medicine, Chung Shan Medical University
    • Other Contributors:
      • Wei-Ting Hsu, medical student
      • Yu-Hsuan Lin, medical student
      • James Cheng-Chung Wei, MD, PhD

    We read with interest the article of Imke Redeker et al.1 The article not only has included large quantity of patients but also performed sensitivity analysis and subgroup analysis of. Authors concluded that glucocorticoids and JAK inhibitors were associated with risk of herpes zoster (HZ) in rheumatoid arthritis (RA) patients. However, there are some concerns that required to be taken into account in order to make the study more comprehensive.
    First of all, the dosage or exposure duration of disease-modifying antirheumatic drugs treatments (DMARDs) has barely mentioned in this study. We know that the purpose of the study might simply be intent to focus on the connection between medicine exposure and the outcome of HZ. Nevertheless, it’s our opinion that dose response relationship should be analyzed to show dose-dependent effect.
    Second, drug-drug interaction is an important issue on all treatment. There’s already some evidence showing certain drugs that may interact with DMARDs. In this research, CYP3A4 inhibitor together with CYP2C19 have been discussed to have a cross action with JAK inhibitors.2 Drugs may change the original medicinal effect proposed to be and thus interfere with the result we get. What’s more, apart from glucocorticoids and methotrexate mentioned in article, we suggest that more kinds of common immunosuppressants should be considered. Especially for RA patients, immunosuppressants such as cyclosporine, leflunomide and mycophenolate...

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    Conflict of Interest:
    None declared.