Tuberculosis and atypical mycobacterial infections in ruxolitinib-treated patients with primary or secondary myelofibrosis or polycythemia vera

Abstract

Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur.

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review

“…26 Two additional cases were reported by Lescuyer et al in 65 patients treated with ruxolitinib during a single institutional experience; 1 (1.5%) patient had MTB and the other (1.5%) had an AMI; both were fatal disseminated infections. 27 In an Italian multicenter study, MTB occurred in 0.7% (3/446) of patients taking ruxolitinib, 28 and in a safety and efficacy analysis of the JUMP trial, the incidence was 0.3%. 29 Although our data cannot determine the exact incidence of patients on ruxolitinib that developed MTB or AMI (FAERS public dashboard reports patients with adverse events, not total number of patients taking the medication), it is known that 0.4% and 0.09% of adverse events associated with ruxolitinib were MTB and AMI, respectively.…”

<p>Tuberculosis Peritonitis During Treatment of Polycythemia Vera with Ruxolitinib</p>

“…28 Our search of the English-written literature identified nine reports of MPN cases affected by MTB infection (Table 1). [9][10][11][12][13][14][15][16][17] Including the present case, the reported cases include 7 of PMF and 3 of PV, including two that progressed to secondary myelofibrosis. Among the 10 patients, 7 had pulmonary tuberculosis and 5 of these 7 cases also had extrapulmonary lesions in lymph nodes, bone, or brain.…”

“…Indeed, an increased risk of VZV reactivation during ruxolitinib treatment has been reported in clinical trials for MPN, [4][5][6] and a more recent retrospective pharmacovigilance review did find an increased risk of MTB and AMI that were sometimes fatal in MPN patients receiving ruxolitinib. 7,8 During ruxolitinib treatment, MPN cases may be complicated by opportunistic infections such as MTB and AMI, [9][10][11][12][13][14][15][16][17] pneumocystis jiroveci pneumonitis, 22 toxoplasma retinitis, 23 Cryptococcus neoformans pneumonitis, 24 and progressive multifocal leukoencephalopathy, 25 and by reactivation of latent viral infection with hepatitis B virus 26 and cytomegalovirus. 27 Thus, optimal anti-infective prophylaxis or monitoring for occult viral infection is needed with the use of ruxolitinib.…”

“…[29][30][31][32][33] Tuberculosis peritonitis may be fatal, as in two cases in Table 1 and also reported previously. 7,16,17 Therefore, it is important to suspect tuberculosis peritonitis, measure the ADA level in ascites as an alternative for differential diagnosis of the disease, and make a decision on empirical treatment, even without histologic or bacteriologic confirmation of mycobacterial infection. 32,33 An IGRA is a widely used in vitro blood test for the diagnosis of MTB infection.…”

“…These include varicella-zoster virus (VZV) reactivation and mycobacterium infection with both typical mycobacterium tuberculosis (MTB) and atypical mycobacterial infections (AMI) in patients with MPNs. [6][7][8] A search of the English-written literature on MTB infection during ruxolitinib treatment for MPNs revealed cases with disseminated tuberculosis, pulmonary tuberculosis, and tuberculosis lymphadenitis, [9][10][11][12][13][14][15][16][17] but no case of tuberculosis peritonitis. Here, we report a rare case of PV complicated by tuberculosis peritonitis while under treatment with ruxolitinib.…”