Thyroid-Associated Orbitopathy

Abstract

We would like to thank Khanna et al.1Khanna D. Chong K.K. Afifiyan N.F. et al.Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy.Ophthalmology. 2010; 117: 133-139Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar for sharing their results using rituximab (RTX) for severe thyroid-associated ophthalmopathy (TAO). We agree that current treatment options do not alter the ultimate course of TAO, and we applaud their efforts to study a newer biologic therapy. The authors correctly point out that the safety profile of RTX compares favorably with that of corticosteroids and treatment guidelines for autoimmune disease call for substantially lower doses and frequencies than those for lymphoma. However, because RTX falls outside most ophthalmologists' bailiwick, its side effects may warrant further discussion. Acute infusion reactions account for the most commonly reported adverse events after RTX treatment and occur most often after the first infusion.2Fleischmann R.M. Safety of biologic therapy in rheumatoid arthritis and other autoimmune diseases: focus on rituximab.Semin Arthritis Rheum. 2009; 38: 265-280Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar The authors' premedication regimen of corticosteroids, acetaminophen, and diphenhydramine minimizes, but does not eliminate, these reactions. Interestingly, the further elevation in preexisting hypertension noted in Patient 5 after the first RTX infusion may have constituted such a reaction. While most acute infusion reactions are not serious, fatal reactions and serum sickness can occur. The B-cell depletion induced by RTX also increases the risk for acute infection. The authors report one patient who developed a urinary tract infection that responded to oral antibiotics, but life-threatening infections can occur, even at the lower doses and frequencies used to treat autoimmune diseases. The few fatal infections reported under these circumstances have occurred in patients with a history of other biologic therapies for autoimmune disease, but RTX likely played a role.3Teichmann L.L. Woenckhaus M. Vogel C. et al.Fatal Pneumocystis pneumonia following rituximab administration for rheumatoid arthritis.Rheumatology (Oxford). 2008; 47: 1256-1257Crossref PubMed Scopus (44) Google Scholar The risk of serious infection appears quite low, and seems to remain stable over subsequent treatment courses.4van Vollenhoven R.F. Emery P. Bingham 3rd, C.O. et al.Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials.J Rheumatol. 2010; 37: 558-567Crossref PubMed Scopus (216) Google Scholar While side effects such as infusion reactions and acute infections should respond to treatment, several patients with autoimmune disease have developed progressive multifocal leukoencephalopathy (PML) after RTX treatment.5Carson K.R. Evens A.M. Richey E.A. et al.Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project.Blood. 2009; 113: 4834-4840Crossref PubMed Scopus (760) Google Scholar The association with this often fatal JC virus reactivation raises some concern. Fortunately, the absolute risk appears quite low. Further, the patients who developed PML after RTX for autoimmune disease had a history of other autoimmune treatments, obscuring the exact role of RTX in causing the PML. Infusion reactions, infection, and PML represent uncommon but significant risks of RTX therapy for TAO. Of course, current treatments for TAO, including surgery and corticosteroids, also carry potentially fatal risks. We agree that B-cell depletion may yield an acceptable risk:benefit ratio for patients with severe TAO refractory to corticosteroids. Ophthalmologists should understand some of the side effects of this drug to participate in patient counseling. The exact indications will continue to evolve as our knowledge regarding the dose, frequency and risks improve. We thank the authors for studying their experience using this therapy. Rituximab Treatment of Patients with Severe, Corticosteroid-Resistant Thyroid-Associated OphthalmopathyOphthalmologyVol. 117Issue 1PreviewTo study the effectiveness of anti-CD20 (rituximab [RTX]; Rituxan; Genentech, Inc., South San Francisco, CA) therapy in patients with severe, corticosteroid (CS)-resistant thyroid-associated ophthalmopathy (TAO). Full-Text PDF Author replyOphthalmologyVol. 117Issue 9PreviewWe appreciate the authors' enthusiasm for the introduction of new treatment strategies directed at thyroid associated orbitopathy (TAO). We share their concerns regarding rational use of anti-B cell therapies and heartily agree that their use warrants further discussion. This dialogue must focus on specific indications for treatment and identifying clinical and laboratory end points of effectiveness. Full-Text PDF