Infliximab for Refractory Cardiac Sarcoidosis

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.

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“…Other therapies that have been used in CS include azathioprine, cyclophosphamide, infliximab, 57 and rarely rituximab (Table 4 ). 104 – 107 …”

Section: Sarcoidotic Myocarditismentioning

confidence: 99%

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

Ammirati

Frigerio

Adler

et al. 2020

Circ: Heart Failure

469

601

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“…Steroids dose, dysrhythmia control, and ejection fraction were improved, respectively, in 20, 12, and 8 patients among responders. 98 Overall, current data suggest the efficacy of IFX in pulmonary, cutaneous, ocular, and multisystemic sarcoidosis and of ADA in cutaneous and ocular sarcoidosis. To date, no available data support the use of other TNFi, such as golimumab 99 in sarcoidosis.…”

Section: Tnf-α Inhibitorsmentioning

confidence: 81%

<p>Refractory Sarcoidosis: A Review</p>

Jammal

Jamilloux

Gerfaud‐Valentin

et al. 2020

TCRM

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Sarcoidosis is a multi-system disease of unknown etiology characterized by granuloma formation in various organs (especially lung and mediastinohilar lymph nodes). In more than half of patients, the disease resolves spontaneously. When indicated, it usually responds to corticosteroids, the first-line treatment, but some patients may not respond or tolerate them. An absence of treatment response is rare and urges for verifying the absence of a diagnosis error, the good adherence of the treatment, the presence of active lesions susceptible to respond since fibrotic lesions are irreversible. That is when second-line treatments, immunosuppressants (methotrexate, leflunomide, azathioprine, mycophenolate mofetil, hydroxychloroquine), should be considered. Methotrexate is the only first-line immunosuppressant validated by a randomized controlled trial. Refractory sarcoidosis is not yet a well-defined condition, but it remains a real challenge for the physicians. Herein, we considered refractory sarcoidosis as a disease in which second-line treatments are not sufficient to achieve satisfying disease control or satisfying corticosteroids tapering. Tumor necrosis alpha inhibitors, third-line treatments, have been validated through randomized controlled trials. There are currently no guidelines or recommendations regarding refractory sarcoidosis. Moreover, criteria defining non-response to treatment need to be clearly specified. The delay to achieve response to organ involvement and drugs also should be defined. In the past ten years, the efficacy of several immunosuppressants beforehand used in other autoimmune or inflammatory diseases was reported in refractory cases series. Among them, anti-CD20 antibodies (rituximab), repository corticotrophin injection, and anti-JAK therapy anti-interleukin-6 receptor monoclonal antibody (tocilizumab) were the main reported. Unfortunately, no clinical trial is available to validate their use in the case of sarcoidosis. Currently, other immunosuppressants such as JAK inhibitors are on trial to assess their efficacy in sarcoidosis. In this review, we propose to summarize the state of the art regarding the use of immunosuppressants and their management in the case of refractory or multidrugresistant sarcoidosis.

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“…The study found that discontinuation of immunosuppression was significantly associated with FDG-PET SUV increase and VT recurrence, and steroid-sparing immunosuppressive agents such as MTX or adalimumab were effective in suppressing inflammation in CS. In November 2019, Harper et al (24) reported 36 patients treated by infliximab for CS refractory to conventional treatment. Twenty-four (66%) patients were categorized as "responders" after infliximab initiation in at least one of the three outcomes categories (steroid-sparing dose, LVEF, and dysrhythmia).…”

Section: Discussionmentioning

confidence: 99%

“…In severe or refractory disease, TNFα antagonists are effective in ocular (13), neurological (14), osseous (15), and pulmonary (16,17), sarcoidosis. In CS, a few cases reports (18)(19)(20)(21)(22) and five cohort studies (23)(24)(25)(26)(27) have shown benefits of CT with or without IT in patients with severe and/or refractory cardiac involvement. Although there has been no randomized controlled study, some articles and expert opinions have suggested that TNFα antagonists for severe or refractory CS might be an option in case of CT or IT failure (28-30).…”

Section: Introductionmentioning

confidence: 99%

Case Report: TNFα Antagonists Are an Effective Therapy in Cardiac Sarcoidosis

Stievenart¹,

Guenno²,

Ruivard³

et al. 2021

Front. Cardiovasc. Med.

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Introduction: Cardiac sarcoidosis (CS) is a life-threatening disease in which clear recommendations are lacking. We report a case series of CS successfully treated by tumor necrosis factor (TNF)α antagonists.Methods: We conducted a single-center retrospective study of our patients with CS treated by TNFα antagonists.Results: Four cases (4/84, 4.7%) were found in our database. Mean age was 40 years (range 34–53 years), and all were Caucasian men. Mean follow-up was 54.75 months (range 25–115 months). All patients received corticosteroid therapy (CT) and immunosuppressive therapy (IT). TNFα antagonists (infliximab or adalimumab) were started after the first or second CS relapse under CT and IT. One patient experienced relapse under TNFα antagonists (isolated decreased left ventricular ejection) and responded to a shorter interval of TNFα antagonist infusion. CT was discontinued in three patients treated with TNFα antagonists without relapse or major cardiac events during follow-up. No serious adverse event occurred in our case series, possibly due to dose sparing and frequent arrest of CT.Conclusion: TNFα antagonists were effective in refractory and/or relapsing CS treated by corticosteroids and/or immunosuppressive agents, without serious adverse events, and should be considered earlier in CS treatment scheme.

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Infliximab for Refractory Cardiac Sarcoidosis

Cited by 60 publications

References 13 publications

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

<p>Refractory Sarcoidosis: A Review</p>

Case Report: TNFα Antagonists Are an Effective Therapy in Cardiac Sarcoidosis

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