Ruxolitinib in Aicardi-Goutières syndrome

Mura, Eleonora; Masnada, Silvia; Antonello, Clara E.; Parazzini, Cecilia; Izzo, Giana; Garau, Jessica; Sproviero, Daisy; Cereda, Cristina; Orcesi, Simona; Veggiotti, Pierangelo; Zuccotti, Gianvincenzo; Dilillo, Dario; Penagini, Francesca; Tonduti, Davide

doi:10.1007/s11011-021-00716-5

Cited by 14 publications

(13 citation statements)

References 19 publications

(16 reference statements)

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“…Data on AEs was available for only one patient (1/3, 33.3%) ( 48 ) who developed creatine kinase fluctuations, hypercholesterinemia, and hypertriglyceridemia, which were transient and controlled by dietary management without the need for JAKi dose reduction or hospitalization. No other AEs were reported.…”

Section: Resultsmentioning

confidence: 99%

Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review

et al. 2022

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IntroductionAutoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.MethodsA systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.ResultsWe report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).ConclusionThe results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.

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Section: Resultsmentioning

confidence: 99%

Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review

et al. 2022

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“…Recently, JAK inhibitors including Ruxolitinib and Baricitinib have been reported to not only control AGS related skin lesions but neurologic function even in cases with severe and longstanding disease [36][37][38]. Other developing regimens, including interferon-α/β receptor blockade, IFN-α targeting, reverse-transcriptase inhibitors and stimulator of interferon genes (STING) antagonist also provide various degree of benefits as these medications suppress IFN signaling [39][40][41][42][43][44]. As targeted therapy became available, clinical suspicion and genetic testing for AGS is especially important for patients presenting with early-onset lupus mimic disease.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus

et al. 2022

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Background Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5. Case presentation Among the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy. Conclusions Genetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment.

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“…At infancy, he was hospitalised due to bronchiolitis and administered levetiracetam and clobazam owing to seizures. The successful use of Janus kinase inhibitors, such as ruxolitinib and baricitinib, to treat AGS was recently reported 13 14. Considering the disease progression, such as persistent seizures, development delay, a poor eye contact, a reticular skin pattern, oxygen dependency, a low cardiac output and persistent lymphocytic leucocytosis, the Janus kinase inhibitor baricitinib (0.2 mg/per kg body weight in two divided doses) was started at infancy, and it was tolerated well by the baby.…”

Section: Treatmentmentioning

confidence: 99%

Aicardi-Goutières syndrome (AGS): recurrent fetal cardiomyopathy and pseudo-TORCH syndrome

et al. 2022

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Aicardi-Goutières syndrome (AGS) induces innate immune activation. It can present with cerebral calcifications and hepatosplenomegaly mimicking congenital infections. The present case report discusses the diagnosis and treatment of a case of fetal cardiomyopathy whose postnatal symptoms resembled TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes and syphilis) infection. The mother had a history of two lost pregnancies due to fetal cardiomyopathy and the same was identified in the current pregnancy. At 34 weeks of gestation, the mother delivered a late preterm male neonate due to intrauterine growth restriction weighing 1590 g with respiratory distress and cardiomyopathy at birth. The neonate had cerebral calcifications, hepatosplenomegaly and thrombocytopenia. As the infant’s TORCH IgM titre was negative, pseudo-TORCH syndrome similar to AGS was suspected. Clinical exome sequencing of the parents and fetus identified no genes for hydrops fetalis or fetal cardiomyopathy; however, the AGSTREX1gene was identified in the neonate, while additional symptoms resembled TORCH infection. The neonate was discharged and has shown improvement with oral baricitinib treatment for the last 9 months.

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Ruxolitinib in Aicardi-Goutières syndrome

Cited by 14 publications

References 19 publications

Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review

Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review

Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus

Aicardi-Goutières syndrome (AGS): recurrent fetal cardiomyopathy and pseudo-TORCH syndrome

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