Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis

Scappaticcio, Lorenzo; Castellana, Marco; Virili, Camilla; Bellastella, Giuseppe; Centanni, Marco; Cannavò, Salvatore; Campennì, Alfredo; Ruggeri, Rosaria M.; Giovanella, Luca; Trimboli, Pierpaolo

doi:10.1007/s40618-019-01105-7

Cited by 48 publications

(61 citation statements)

References 34 publications

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“…The frequency and distribution of thyroid malfunctions following ALZ is well in line with previous reports, 26 although somewhat higher than in a recent systematic review, with a pooled prevalence of 33% after a median follow-up of 57 months. 29 The frequency of thyroid disease following AHSCT (19%) was significantly lower than after treatment with ALZ, but higher than the 4.0%-17% described previously. 32 The use of different conditioning regimens and differences in DMD treatment prior to AHSCT could affect the occurrence of secondary autoimmunity and methodological differences in identifying and classifying adverse events could also contribute to the discrepancies between different studies.…”

Section: Discussionmentioning

confidence: 58%

“…Late adverse events of ALZ and AHSCT have been described after treatment of MS, including both infectious and autoimmune complications as well as treatment-related mortality. [26][27][28][29][30][31] Late adverse events of grade 3 or higher were uncommon in both cohorts. Nearly half of the patients treated with ALZ had an autoimmune adverse event, compared with 20% in the AHSCT group; this constitutes the major difference in the late adverse events between the groups.…”

Section: Discussionmentioning

confidence: 88%

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Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Zhukovsky

Sandgren

Silfverberg

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveTo compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing–remitting multiple sclerosis.MethodsPatients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly.ResultsThe Kaplan-Meier estimates of the primary outcome measure ‘no evidence of disease activity’ was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005.ConclusionsIn this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining ‘no evidence of disease activity’. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 88%

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Zhukovsky

Sandgren

Silfverberg

et al. 2020

J Neurol Neurosurg Psychiatry

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“…The detection of thyroid autoantibodies has been inconsistent and has no obvious predictive role, unlike the situation with α-IFN [26]. It is also now clear that alemtuzumab, which is used in multiple sclerosis to deplete T cells and frequently leads to Graves' disease during the phase of immune reconstitution, may cause HT in around 15% of cases, as well as painless thyroiditis [27]. The preferential occurrence of Graves' disease may reflect the association of this type of immune reconstitution with other autoantibody-mediated autoimmune diseases.…”

Section: Environmental Factorsmentioning

confidence: 99%

An update on the pathogenesis of Hashimoto’s thyroiditis

Weetman

2020

J Endocrinol Invest

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It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto’s thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tolerance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT.

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“…It is also of interest that some pathways (i.e. the cytokine and hyperactivation of Th1 helper cells responses) of immune responses to virus infection are observed in thyroid disorders [i.e classical autoimmune thyroid diseases (AITD), interferon-alpha-related thyroid disease, immune checkpoint inhibitor mediated thyroiditis, alemtuzumab-induced thyroid dysfunctions] [17,[21][22][23][24]]. Yet, clinicians are very familiar with the evidence that infection can be identified as an environmental stimulus precipitating or accelerating AITD development and the cause of subacute thyroiditis [17,25].…”

Section: Introductionmentioning

confidence: 99%

Impact of COVID-19 on the thyroid gland: an update

Scappaticcio

Pitoia

Esposito

et al. 2020

Rev Endocr Metab Disord

189

195

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Coronavirus disease 2019 (COVID-19) is the pandemic of the new millennium. COVID-19 can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. Data on the relationship between COVID-19 and thyroid have been emerging, and rapidly increasing since March 2020. The thyroid gland and the virus infection with its associated inflammatory-immune responses are known to be engaged in complex interplay. SARS-CoV-2 uses ACE2 combined with the transmembrane protease serine 2 (TMPRSS2) as the key molecular complex to infect the host cells. Interestingly, ACE2 and TMPRSS2 expression levels are high in the thyroid gland and more than in the lungs. Our literature search provided greater evidence that the thyroid gland and the entire hypothalamic–pituitary–thyroid (HPT) axis could be relevant targets of damage by SARS-CoV-2. Specifically, COVID-19-related thyroid disorders include thyrotoxicosis, hypothyroidism, as well as nonthyroidal illness syndrome. Moreover, we noticed that treatment plans for thyroid cancer are considerably changing in the direction of more teleconsultations and less diagnostic and therapeutical procedures. The current review includes findings that could be changed soon by new results on the topic, considering the rapidity of worldwide research on COVID-19.

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Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis

Cited by 48 publications

References 34 publications

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing–remitting multiple sclerosis: an observational study

An update on the pathogenesis of Hashimoto’s thyroiditis

Impact of COVID-19 on the thyroid gland: an update

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