A systematic review of the rates of completion of treatment and activation of disease in patients found to have latent tuberculosis infections after testing and before placement on Anti TNF-Alpha Blockers Open Access
Kinane, Catriona (Spring 2018)
Abstract
Background: Before a patient is placed on tumor necrosis factor (TNF)-alpha blockers (TNFAB) for treatment of rheumatoid arthritis (RA) or other autoimmune conditions, they are screened for latent tuberculosis infection (LTBI). If a patient is found to have LTBI, they are to receive treatment with drugs shown to be effective in preventing progression to TB disease, often given under directly observed therapy. These recommendations by health agencies and professional organizations are meant to protect persons who receive immunosuppressive therapy with TNFAB from the underlying risk of developing active TB disease.
Methods: A systematic review of the literature was done using PubMed to identify English publications with data for completion of LTBI therapy and for TB disease progression in patients who received TNFAB for treatment of their autoimmune diseases. After these publications were identified, the risk ratios activation of TB disease and proportion of completion of treatment were determined using Open Epi software. These results were entered into Stata software, and an overall probability of completion of LTBI therapy and of disease activation was calculated using the formula for risk ratio.
Results: There were high rates of completion of treatment for LTBI. The overall risk ratio of activation of TB if a patient was found to have LTBI was 3.299 with a 95% confidence interval (CI) of 1.195 to 9.105. Patients who were placed on TNFAB and had a positive test for LTBI where at a higher risk of developing TB than those who had a negative baseline LTBI test. However, the overall risk of TB disease, given a person had completed treatment for LTBI was 1.094 (CI 0.402, 2.979).
Conclusions: Those patients prescribed LTBI treatment after a positive screening test (before placement on TNFAB) are likely to complete the treatment regimen. In addition, being treated for LTBI was not associated with a statistically significant risk of progression to active TB, suggesting a protective effect of treatment for LTBI. Results could have underestimated the benefit of LTBI therapy in persons with false-negative tests for LTBI, possibly related to immunosuppression.
Table of Contents
Background 1
Methods 5
Results 10
Discussion 12
Conclusion 16
Figures 17
Figure 1: Systematic review flow chart 17
Figure 2 Calculated risk of developing TB in patients treated for LTBI in publications that provided activation data 18
Figure 3 Publication bias for all publications that provided activation data 19
Figure 4 Calculated risk of developing TB in patients treated for LTBI in publications that provided completion data 20
Figure 5 publication bias for developing TB in patients treated for LTBI in publications that provided completion data 21
Tables 22
Table 1A Publications that provide data for disease activation in patients that were found to have LTBI infection compared to those that were found to be negative duration 22
Table 1B Publications that provide data for disease completion for patients found to have LTBI and were placed on treatment 23
Table 1C Publications that provide data for disease completion and activation of disease in patients that were found to have LTBI and were placed on treatment 24
Table 2: risk of reactivation given a person is found to be positive for LTBI with Stata provided statistical test values 25
Table 3: Publication Bias table for Activation of TB disease when comparing Activation in Patients found with LTBI and no LTBI with Stata provided statistical test values 25
Table 4: Filled model of Publication Bias for Activation of TB disease when Comparing Activation in patients found with LTBI and no LTBI with Stata provided statistical test values 25
Table 5: Risk of Activation given a person is Found to be Positive for LTBI with Stata provided statistical test values 26
Table 6: Publication Bias Table for Activation of TB Disease when Comparing Activation in Patients found with LTBI and no LTBI with Stata provided statistical test values 26
Table 7: Filled model of Publication Bias for Activation of TB Disease when Comparing Activation in Patients found with LTBI and no LTBI with STATA provided statistical test values 26
Table 8: Percentile of Completion and Weight of Importance per paper for LTBI Treatment with Stata provided statistical test values 27
References 28
Appendix 1: Open epi outputs 33
Appendix 2: Stata code 39
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