Tocilizumab for the Management of Thyroid-Associated Orbitopathy

Abstract

Purpose: To describe the efficacy of tocilizumab in the treatment of a cohort of patients with active thyroid-associated orbitopathy. Methods: Patients were identified with active thyroid-associated orbitopathy who were intolerant of or had progression of disease despite systemic corticosteroids and subsequently were treated with tocilizumab between January 2015 and December 2020. Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels were assessed prior to initiation of tocilizumab, following the first dose, and after the completion of treatment. Results: Eleven patients were candidates for and underwent treatment with tocilizumab, 9 of which met criteria for analysis. Average age was 55.6 years. Average time between onset of active thyroid-associated orbitopathy and completion of tocilizumab was 6.5 months. Average number of infusions was 4.2. There was a statistically significant reduction in Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels when comparing pre-treatment values (mean Clinical Activity Score 6.78 ± 1.09, mean Thyroid-Associated Ophthalmopathy Scale score 10.2 ± 1.92, mean thyroid-stimulating immunoglobulin level 440.6 [%]) to values immediately following completion of treatment (mean Clinical Activity Score 0.44 ± 0.53, mean difference 6.3 points, p < 0.001 [95% CI, 5.5–7.2]; mean Thyroid-Associated Ophthalmopathy Scale score 1.2 ± 1.09, mean difference 9.0 points, p < 0.001 [95% CI, 7.2–10.8]; mean thyroid-stimulating immunoglobulin level 200.7 [%], mean difference 239.9 [%], p = 0.001 [95% CI, 124.3–355.4]). One patient had elevation of cholesterol following therapy induction. Patients were followed for an average of 23.6 months after treatment. No patients had recurrence of active disease after completion of tocilizumab. Conclusions: This study supports the use of tocilizumab as a therapy for the inflammatory phase of thyroid-associated orbitopathy.

Monoclonal Antibodies for the Treatment of Graves Orbitopathy: Precision Medicine?

“…1 shows that 76 articles of the 954 screened records were included in the review. The literature on the use of Mabs for treating GO has been centered on blockage of IL-6 (Tocilizumab), 34,39,41,49,50,53,56,[58][59][60]63,64,[68][69][70][71][72]79,80,84,87,90,[96][97][98] anti-CD20 lymphocytes (Rituximab), [26][27][28][29][30][31][32][33]35,37,38,40,[42][43][44][45][46][47][48]51,54,55,61,62,65,…”

“…1 shows that 76 articles of the 954 screened records were included in the review. 25–101 The literature on the use of Mabs for treating GO has been centered on blockage of IL-6 (Tocilizumab), 34,39,41,49,50,53,56,58–60,63,64,68–72,79,80,84,87,90,96–98 anti-CD20 lymphocytes (Rituximab), 26–33,35,37,38,40,42–48,51,54,55,61,62,65,67,73,89 and IGF1R (Teprotumumab). 52,66,74–78,82,85,86,88,91,92,94,95,99–101 Three articles have described Mabs that block TNF-α, 25,36,83 and one article has described Mabs that block the B-lymphocyte stimulator (BLyS) protein (Belimumab).…”

Autoimmune disorders and thyroid function in patients with rheumatoid arthritis after biological treatment

“…A recent study found statistically significant reductions in the CAS, Thyroid-Related Ophthalmopathy Score and Thyroid Stimulating Immunoglobulin levels when comparing pre-treatment values. None of the patients relapsed to active disease after stopping tocilizumab treatment [69].…”

Perspectives on Antibody-Based Thyroid-Associated Orbitopathy Treatments

“…Use of tocilizumab incurs such risks as immunosuppression, elevated cholesterol, elevated hepatic transaminases, and cytopenias, but as used in the context of TAO, adverse events of these type are generally mild to moderate in severity. 9,[31][32][33] Though one could argue that systemic immunosuppression is a significant downside to tocilizumab, given the relatively brief duration of therapy (4-5 monthly infusions) we feel this is a rather small risk as long as appropriate pretreatment laboratory investigation is completed. Given the clear benefits of this agent, for which TAO is currently an off-label use, development of an IL-6/IL-6 receptor targeting agent specifically FDA-approved to address TAO would be a valuable addition to the therapeutic landscape.…”

“…As noted in the studies highlighted above, tocilizumab led to significant decrease in systemic inflammatory markers of TAO, namely TR antibodies 32 and TSI. 9 The significance of these reductions even after just one infusion suggests that tocilizumab is specifically acting to reduce the immunologic activity of TAO. Furthermore, by providing systemic immunosuppressive activity through its effects on IL-6, as discussed above, tocilizumab may be especially useful in patients with prominent extra-orbital manifestations.…”