<i>Pneumocystis jiroveci</i>pneumonitis complicating ruxolitinib therapy

Lee, Samantha C.; Feenstra, John; Georghiou, Paul R.

doi:10.1136/bcr-2014-204950

Cited by 37 publications

(23 citation statements)

References 10 publications

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“…Eight papers were excluded for the following reasons: pooled analysis ( n = 1), follow‐up of phase I or II trial ( n = 1), sub‐analyses ( n = 2), data on extension phase study with a shorter follow‐up ( n = 2), redundant publications ( n = 2). Five phase III RCTs (3 phase IIIa with their most recently published extended phase (750 patients) and 2 phase IIIb RCTs (283 patients)), 6 phase IV studies (1524 patients) and 28 case report publications (31 patients, of whom 4 were included also in phase III studies and 1 in phase IV study) were included in this systematic review.…”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, this is the first systematic review and meta‐analysis that has been performed with the primary aim to evaluate the incidence and severity of infectious complications in MPN patients treated with ruxolitinib. Available evidence is insufficient to accurately estimate the risk of infections in ruxolitinib‐treated patients, but suggests that the incidence of opportunistic and viral infections in ruxolitinib‐treated patients may be clinically relevant …”

Section: Discussionmentioning

confidence: 99%

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Ruxolitinib‐associated infections: A systematic review and meta‐analysis

et al. 2017

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Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

et al. 2017

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“…However, as clinical experience expanded in the non-trial setting, multiple episodes of infectious complications, often atypical, following ruxolitinib usage were rapidly reported to some initial concern. These included individual case reports of bilateral toxoplasma retinitis; reactivation of hepatitis B, Cryptococcus neoformans pneumonitis, Pneumocystis jiroveci infection and JC-virus-associated progressive multifocal encephalopathy [19][20][21][22]48]. One case report also tentatively reports a masking of necrotizing fasciitis in a patient on JAKi therapy [49].…”

Section: Current Status Of Jak Inhibitors Focus On Infectious Complicmentioning

confidence: 93%

Immunological Consequences of JAK Inhibition: Friend or Foe?

McLornan

Khan

Harrison

2015

Curr Hematol Malig Rep

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Over the last decade, unparalleled advances have been made within the field of 'Philadelphia chromosome'-negative myeloproliferative neoplasms (MPN) regarding both disease pathogenesis and therapeutic targeting. The discovery of deregulated JAK-STAT signalling in MPN led to the rapid development of JAK inhibitor agents, targeting both mutated and wild-type JAK, which have significantly altered the therapeutic paradigm for patients with MPN. Although the largest population treated with these agents incorporates those with myelofibrosis, increasing data supports potential usage in other MPNs such as essential thromocythaemia and polycythaemia vera. Many MPNs are associated with a hyperinflammatory state and deregulation of immune homeostasis. Over the last few years, research has focused on attempting to decipher the complex and context-dependent changes that contribute to this immune deregulation. Moreover, very recent studies have demonstrated significant JAK inhibitor-mediated effects within the T cell, natural killer cell and dendritic cell compartments following exposure to JAK inhibitors. In parallel, case reports of infections occurring following exposure to ruxolitinib, many of which are atypical, have focused research efforts on delineating JAK inhibitor-associated immunological consequences. Within this review article, we will describe what is currently known about MPN-associated immune deregulation and JAK inhibitor-mediated immunomodulation.

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“…Although such effects may have played a role in isolated cases of serious opportunistic infections in patients on ruxolitinib therapy, including progressive multifocal leukoencephalopathy (PML) [84], reactivation of hepatitis B virus [85], pneumonia [86], disseminated tuberculosis [87], reactivation of herpes simplex virus [88] and Pneumocystis jiroveci pneumonitis [89], the relationship of these infections with ruxolitinib treatment remains unclear. Common infections that occurred during randomized treatment in patients in the ruxolitinib arm of COMFORT-I were urinary tract infections and herpes zoster (Table 6) [32].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis

Tam

Verstovšek

2015

Future Oncol.

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The JAK 1 and JAK2 inhibitor ruxolitinib has approved indications in myelofibrosis, a BCR-ABL1-negative myeloproliferative neoplasm associated with progressive bone marrow fibrosis and shortened survival. In Phase III clinical studies, ruxolitinib provided rapid and durable improvement of myelofibrosis-related splenomegaly and symptoms irrespective of mutation status, and was associated with a survival advantage compared with placebo or best available therapy. Because of dose-dependent cytopenias, blood count monitoring and dose titration are important to optimize therapy. Specific precautions apply to the treatment of patients with or at risk of serious infections. Discontinuation of ruxolitinib generally leads to symptom return within 1 week. Ruxolitinib also is approved for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

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Pneumocystis jirovecipneumonitis complicating ruxolitinib therapy

Cited by 37 publications

References 10 publications

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

Immunological Consequences of JAK Inhibition: Friend or Foe?

Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis

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