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We have read with great interest the work of Ulf Lindström et al studying on comparing the risk of anterior uveitis (AU) in spondyloarthritis (SpA) during treatment with secukinumab versus tumour necrosis factor inhibitors (TNFi). They concluded that secukinumab appears to be associated with a higher risk of AU, compared with the monoclonal TNFi and a similar risk compared with etanercept1. However, we believe that some concerns should be discussed in this important study.
First of all, the recruited SpA patients starting secukinumab or a TNFi between 1 Jan 2015 and 31 December 2018 were identified and the follow-up were most at the end of study 31 December 2018. However, there would be certain bias on the comparison of the rate of AU-diagnoses between the patients during treatment with secukinumab or TNFi in the late 2018 to the patients during treatment with TNFi or secukinumab in the early 2015. It would be more proper to adjust the treatment starting time. Furthermore, subgroups for the different starting year were also recommended to analyze.
Secondly, conventional synthetic DMARDs, such as methotrexate (MTX) and sulfasalazine (SSZ), were sometimes used together with secukinumab or a TNFi in part of the patients. For both SSZ and MTX, a reduction in the AAU flare rate and sight-threatening complications has been reported especially on the course of HLA-B27-positive anterior uveitis2-4. AS a result, concomitant csDMARDs with secukinumab or a TNFi could be...
Secondly, conventional synthetic DMARDs, such as methotrexate (MTX) and sulfasalazine (SSZ), were sometimes used together with secukinumab or a TNFi in part of the patients. For both SSZ and MTX, a reduction in the AAU flare rate and sight-threatening complications has been reported especially on the course of HLA-B27-positive anterior uveitis2-4. AS a result, concomitant csDMARDs with secukinumab or a TNFi could be one of the obvious confounders in this study. The baseline of the DMARDs usage should also be adjusted.
Thirdly, AU, chronic and easy to recurrent, often require receiving topical steroid and mydriatic eye drops during acute uveitis recurrence. Regular ophthalmology visit is a must for the AU patients. In this study AU was easy to be under-diagnosed. It would be more proper to adjust the ophthalmology visit for confounding. It would be more proper to determine the accuracy of their AU definition algorithm, such as Dublin Uveitis Evaluation Tool (DUET) which have excellent sensitivity (96 %) and specificity (97 %)5.Moreover, in-depth discussion of confounding effect should be made. These factors include Serum antistreptolysin-O titers and positive HLA-B27, and number of peripheral joints6.
Finally, some residual confounders for uveitis might still existed, including patients’ life style and environmental factors, esp. air pollution7. These possible confounders should be considered when interpreting the results.
This work was supported by funding from the National Natural Science Foundation of China Grants (82004238).
The authors declare no conflict of interest.
1. Lindström U, Bengtsson K, Olofsson T, et al. Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care: does the choice of biological therapy matter? Annals of the rheumatic diseases 2021 doi: 10.1136/annrheumdis-2021-220420 [published Online First: 2021/06/17]
2. Muñoz-Fernández S, Hidalgo V, Fernández-Melón J, et al. Sulfasalazine reduces the number of flares of acute anterior uveitis over a one-year period. The Journal of rheumatology 2003;30(6):1277-9. [published Online First: 2003/06/05]
3. Muñoz-Fernández S, García-Aparicio AM, Hidalgo MV, et al. Methotrexate: an option for preventing the recurrence of acute anterior uveitis. Eye (London, England) 2009;23(5):1130-3. doi: 10.1038/eye.2008.198 [published Online First: 2008/08/09]
4. Zu Hoerste MM, Walscheid K, Tappeiner C, et al. The effect of methotrexate and sulfasalazine on the course of HLA-B27-positive anterior uveitis: results from a retrospective cohort study. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2018;256(10):1985-92. doi: 10.1007/s00417-018-4082-x [published Online First: 2018/08/03]
5. Khan MA, Haroon M, Rosenbaum JT. Acute Anterior Uveitis and Spondyloarthritis: More Than Meets the Eye. Current rheumatology reports 2015;17(9):59. doi: 10.1007/s11926-015-0536-x [published Online First: 2015/08/04]
6. D'Ambrosio EM, La Cava M, Tortorella P, et al. Clinical Features and Complications of the HLA-B27-associated Acute Anterior Uveitis: A Metanalysis. Seminars in ophthalmology 2017;32(6):689-701. doi: 10.3109/08820538.2016.1170158 [published Online First: 2016/07/13]
7. Bai YC, Wang CY, Lin CL, et al. Association Between Air Pollution and the Risk of Uveitis: A Nationwide, Population-Based Cohort Study. Frontiers in immunology 2021;12:613893. doi: 10.3389/fimmu.2021.613893 [published Online First: 2021/04/06]