Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors
ATC code: L01EJ01
Ruxolitinib is a selective inhibitor of the Janus Associated Kinases (JAKs) JAK1 and JAK2 (IC50 values of 3.3 nM and 2.8 nM for JAK1 and JAK2 enzymes, respectively). These mediate the signalling of a number of cytokines and growth factors that are important for haematopoiesis and immune function.
Ruxolitinib inhibits JAK-STAT signalling and cell proliferation of cytokine-dependent cellular models of haematological malignancies, as well as of Ba/F3 cells rendered cytokine-independent by expressing the JAK2V617F mutated protein, with IC50 ranging from 80 to 320 nM.
JAK-STAT signalling pathways play a role in regulating the development, proliferation, and activation of several immune cell types important for GvHD pathogenesis.
In a thorough QT study in healthy subjects, there was no indication of a QT/QTc prolonging effect of ruxolitinib in single doses up to a supratherapeutic dose of 200 mg, indicating that ruxolitinib has no effect on cardiac repolarisation.
Two randomised phase 3, open-label, multi-centre studies investigated Jakavi in patients 12 years of age and older with acute GvHD (REACH2) and chronic GvHD (REACH3) after allogeneic haematopoietic stem cell transplantation (alloSCT) and insufficient response to corticosteroids and/or other systemic therapies. The starting dose of Jakavi was 10 mg twice daily.
In REACH2, 309 patients with grade II to IV corticosteroid-refractory, acute GvHD were randomised 1:1 to Jakavi or BAT. Patients were stratified by severity of acute GvHD at the time of randomisation. Corticosteroid refractoriness was determined when patients had progression after at least 3 days, failed to achieve a response after 7 days or failed corticosteroid taper.
BAT was selected by the investigator on a patient-by-patient basis and included anti-thymocyte globulin (ATG), extracorporeal photopheresis (ECP), mesenchymal stromal cells (MSC), low dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), etanercept, or infliximab.
In addition to Jakavi or BAT, patients could have received standard allogeneic stem cell transplantation supportive care including anti-infective medicinal products and transfusion support. Ruxolitinib was added to continued use of corticosteroids and/or calcineurin inhibitors (CNIs) such as cyclosporine or tacrolimus and/or topical or inhaled corticosteroid therapies per institutional guidelines.
Patients who received one prior systemic treatment other than corticosteroids and CNI for acute GvHD were eligible for inclusion in the study. In addition to corticosteroids and CNI, prior systemic medicinal product for acute GvHD was allowed to continue only if used for acute GvHD prophylaxis (i.e. started before the acute GvHD diagnosis) as per common medical practice.
Patients on BAT could cross over to ruxolitinib after day 28 if they met the following criteria:
Tapering of Jakavi was allowed after the day 56 visit for patients with treatment response.
Baseline demographics and disease characteristics were balanced between the two treatment arms. The median age was 54 years (range 12 to 73 years). The study included 2.9% adolescent, 59.2% male and 68.9% white patients. The majority of enrolled patients had malignant underlying disease.
The severity of acute GvHD was grade II in 34% and 34%, grade III in 46% and 47%, and grade IV in 20% and 19% of the Jakavi and BAT arms, respectively.
The reasons for patients' insufficient response to corticosteroids in the Jakavi and BAT arms were i) failure in achieving a response after 7 days of corticosteroid treatment (46.8% and 40.6%, respectively), ii) failure of corticosteroid taper (30.5% and 31.6%, respectively) or iii) disease progression after 3 days of treatment (22.7% and 27.7%, respectively).
Among all patients, the most common organs involved in acute GvHD were skin (54.0%) and lower gastrointestinal tract (68.3%). More patients in the Jakavi arm had acute GvHD involving skin (60.4%) and liver (23.4%), compared to the BAT arm (skin: 47.7% and liver: 16.1%).
The most frequently used prior systemic acute GvHD therapies were corticosteroids+CNIs (49.4% in the Jakavi arm and 49.0% in the BAT arm).
The primary endpoint was the overall response rate (ORR) on day 28, defined as the proportion of patients in each arm with a complete response (CR) or a partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response based on investigator assessment following the criteria by Harris et al. (2016).
The key secondary endpoint was the proportion of patients who achieved a CR or PR at day 28 and maintained a CR or PR at day 56.
REACH2 met its primary objective. ORR at day 28 of treatment was higher in the Jakavi arm (62.3%) compared to the BAT arm (39.4%). There was a statistically significant difference between the treatment arms (stratified Cochrane-Mantel-Haenszel test p<0.0001, two-sided, OR: 2.64; 95% CI: 1.65, 4.22).
There was also a higher proportion of complete responders in the Jakavi arm (34.4%) compared to BAT arm (19.4%).
Day-28 ORR was 76% for grade II GvHD, 56% for grade III GvHD, and 53% for grade IV GvHD in the Jakavi arm, and 51% for grade II GvHD, 38% for grade III GvHD, and 23% for grade IV GvHD in the BAT arm.
Among the non-responders at day 28 in the Jakavi and BAT arms, 2.6% and 8.4% had disease progression, respectively.
Overall results are presented in Table 6.
Table 6. Overall response rate at day 28 in REACH2:
| Jakavi N=154 | BAT N=155 | |||
|---|---|---|---|---|
| n (%) | 95% CI | n (%) | 95% CI | |
| Overall response | 96 (62.3) | 54.2, 70.0 | 61 (39.4) | 31.6, 47.5 |
| OR (95% CI) | 2.64 (1.65, 4.22) | |||
| p-value (2-sided) | p<0.0001 | |||
| Complete response | 53 (34.4) | 30 (19.4) | ||
| Partial response | 43 (27.9) | 31 (20.0) | ||
The study met its key secondary endpoint based on the primary data analysis. Durable ORR at day 56 was 39.6% (95% CI: 31.8, 47.8) in the Jakavi arm and 21.9% (95% CI: 15.7, 29.3) in the BAT arm. There was a statistically significant difference between the two treatment arms (OR: 2.38; 95% CI: 1.43, 3.94; p=0.0007). The proportion of patients with a CR was 26.6% in the Jakavi arm versus 16.1% in the BAT arm. Overall, 49 patients (31.6%) originally randomised to the BAT arm crossed over to the Jakavi arm.
In REACH3, 329 patients with moderate or severe corticosteroid-refractory, chronic GvHD were randomised 1:1 to Jakavi or BAT. Patients were stratified by severity of chronic GvHD at the time of randomisation. Corticosteroid refractoriness was determined when patients had lack of response or disease progression after 7 days, or had disease persistence for 4 weeks or failed corticosteroid taper twice.
BAT was selected by the investigator on a patient-by-patient basis and included extracorporeal photopheresis (ECP), low dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, or ibrutinib.
In addition to Jakavi or BAT, patients could have received standard allogeneic stem cell transplantation supportive care including anti-infective medicinal products and transfusion support. Continued use of corticosteroids and CNIs such as cyclosporine or tacrolimus and topical or inhaled corticosteroid therapies were allowed per institutional guidelines.
Patients who received one prior systemic treatment other than corticosteroids and/or CNI for chronic GvHD were eligible for inclusion in the study. In addition to corticosteroids and CNI, prior systemic medicinal product for chronic GvHD was allowed to continue only if used for chronic GvHD prophylaxis (i.e. started before the chronic GvHD diagnosis) as per common medical practice.
Patients on BAT could cross over to ruxolitinib on day 169 and thereafter due to disease progression, mixed response, or unchanged response, due to toxicity to BAT, or due to chronic GvHD flare.
Efficacy in patients that transition from active acute GvHD to chronic GvHD without tapering off corticosteroids and any systemic treatment is unknown. Efficacy in acute or chronic GvHD after donor lymphocyte infusion (DLI) and in patients who did not tolerate steroid treatment is unknown.
Tapering of Jakavi was allowed after the day 169 visit.
Baseline demographics and disease characteristics were balanced between the two treatment arms. The median age was 49 years (range 12 to 76 years). The study included 3.6% adolescent, 61.1% male and 75.4% white patients. The majority of enrolled patients had malignant underlying disease.
The severity at diagnosis of corticosteroid-refractory chronic GvHD was balanced between the two treatment arms, with 41% and 45% moderate, and 59% and 55% severe, in the Jakavi and the BAT arms, respectively.
Patients' insufficient response to corticosteroids in the Jakavi and BAT arm were characterised by i) a lack of response or disease progression after corticosteroid treatment for at least 7 days at 1 mg/kg/day of prednisone equivalents (37.6% and 44.5%, respectively), ii) disease persistence after 4 weeks at 0.5 mg/kg/day (35.2% and 25.6%), or iii) corticosteroid dependency (27.3% and 29.9%, respectively).
Among all patients, 73% and 45% had skin and lung involvement in the Jakavi arm, compared to 69% and 41% in the BAT arm.
The most frequently used prior systemic chronic GvHD therapies were corticosteroids only (43% in the Jakavi arm and 49% in the BAT arm) and corticosteroids+CNIs (41% patients in the Jakavi arm and 42% in the BAT arm).
The primary endpoint was the ORR on day 169, defined as the proportion of patients in each arm with a CR or a PR without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response based on investigator assessment per National Institutes of Health (NIH) criteria.
A key secondary endpoint was failure free survival (FFS), a composite time to event endpoint, incorporating the earliest of the following events: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) non-relapse mortality, or iii) addition or initiation of another systemic therapy for chronic GvHD.
REACH3 met its primary objective. At the time of primary analysis (data cut-off date: 08-May-2020), the ORR at week 24 was higher in the Jakavi arm (49.7%) compared to the BAT arm (25.6%). There was a statistically significant difference between the treatment arms (stratified Cochrane-Mantel- Haenszel test p<0.0001, two-sided, OR: 2.99; 95% CI: 1.86, 4.80). Results are presented in Table 7.
Among the non-responders at day 169 in the Jakavi and BAT arms, 2.4% and 12.8% had disease progression, respectively.
Table 7. Overall response rate at day 169 in REACH3:
| Jakavi N=165 | BAT N=164 | |||
|---|---|---|---|---|
| n (%) | 95% CI | n (%) | 95% CI | |
| Overall response | 82 (49.7) | 41.8, 57.6 | 42 (25.6) | 19.1, 33.0 |
| OR (95% CI) | 2.99 (1.86, 4.80) | |||
| p-value (2-sided) | p<0.0001 | |||
| Complete response | 11 (6.7) | 5 (3.0) | ||
| Partial response | 71 (43.0) | 37 (22.6) | ||
The key secondary endpoint, FFS, demonstrated a statistically significant 63% risk reduction of Jakavi versus BAT (HR: 0.370; 95% CI: 0.268, 0.510, p<0.0001). At 6-months, the majority of FFS events were “addition or initiation of another systemic therapy for cGvHD” (probability of that event was 13.4% vs 48.5% for the Jakavi and the BAT arms, respectively). Results for “relapse of underlying disease” and non-relapse mortality (NRM) were 2.46% vs 2.57% and 9.19% vs 4.46%, in the Jakavi and the BAT arms, respectively. No difference of cumulative incidences between treatment arms was observed when focusing on NRM only.
The European Medicines Agency has waived the obligation to submit the results of studies with Jakavi in all subsets of the paediatric population for the treatment of MF and PV. In GvHD paediatric patients above 2 years of age, the safety and efficacy of Jakavi are supported by evidence from the randomised phase 3 studies REACH2 and REACH3 and from the open-label, single-arm phase 2 studies REACH4 and REACH5 (see section 4.2 for information on paediatric use). The single-arm design does not isolate the contribution of ruxolitinib to overall efficacy.
In REACH4, 45 paediatric patients with grade II to IV acute GvHD were treated with Jakavi and corticosteroids +/- CNIs to assess the safety, efficacy and pharmacokinetics of Jakavi. Patients were enrolled into 4 groups based on age (Group 1 [≥12 years to <18 years, N=18], Group 2 [≥6 years to <12 years, N=12], Group 3 [≥2 years to <6 years, N=15] and Group 4 [≥28 days to <2 years, N=0]). The doses tested were 10 mg twice daily for Group 1, 5 mg twice daily for Group 2 and 4 mg/m² twice daily for Group 3 and patients were treated for 24 weeks or until discontinuation. Jakavi was administered as either a 5 mg tablet or a capsule/oral solution for paediatric patients <12 years.
Patients were enrolled with either steroid-refractory or treatment-naïve disease status. Patients were considered steroid refractory as per institutional criteria or per physician decision in case institutional criteria were not available and were permitted to have received no more than one additional prior systemic treatment for acute GvHD in addition to corticosteroids. Patients were considered treatment naïve if they had not received any prior systemic treatment for acute GvHD (except for a maximum 72 hours prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of acute GvHD). In addition to Jakavi, patients were treated with systemic corticosteroids and/or CNI (cyclosporine or tacrolimus) and topical corticosteroid therapies were also allowed per institutional guidelines. In REACH4, 40 patients (88.9%) received concomitant CNIs. Patients could also have received standard allogeneic stem cell transplantation supportive care including anti-infective medicinal products and transfusion support. Jakavi was to be discontinued in case of lack of response to acute GvHD treatment at day 28.
Tapering of Jakavi was allowed after the day 56 visit.
Male and female patients accounted for 62.2% (n=28) and for 37.8% (n=17) of patients, respectively. Overall, 27 patients (60.0%) had underlying malignancy, most frequently leukaemia (26 patients, 57.8%). Among the 45 paediatric patients enrolled in REACH4, 13 (28.9%) had treatment-naïve acute GvHD and 32 (71.1%) had steroid-refractory acute GvHD. At baseline 64.4% of patients had grade II, 26.7% had grade III and 8.9% had grade IV acute GvHD.
The overall response rate (ORR) at day 28 (primary efficacy endpoint) in REACH4 was 84.4% (90% CI: 72.8, 92.5) in all patients, with CR in 48.9% of patients and PR in 35.6% of patients. In terms of pre-treatment status, the ORR at day 28 was 90.6% in steroid refractory (SR) patients.
Rate of durable ORR at day 56 (key secondary endpoint) measured by the proportion of patients who achieved a CR or PR at day 28 and maintained a CR or PR at day 56 was 66.7% in all REACH4 patients, and 68.8% in SR patients.
In REACH5, 45 paediatric patients with moderate or severe chronic GvHD were treated with Jakavi and corticosteroids +/- CNIs to assess safety, efficacy and pharmacokinetics of Jakavi treatment. Patients were enrolled into 4 groups based on age (Group 1 [≥12 years to <18 years, N=22], Group 2 [≥6 years to <12 years, N=16], Group 3 [≥2 years to <6 years, N=7] and Group 4 [≥28 days to <2 years, N=0]). The doses tested were 10 mg twice daily for Group 1, 5 mg twice daily for Group 2 and 4 mg/m² twice daily for Group 3 and patients were treated for 39 cycles/156 weeks or until discontinuation. Jakavi was administered as either a 5 mg tablet or an oral solution for paediatric patients <12 years.
Patients were enrolled with either steroid-refractory or treatment-naïve disease status. Patients were considered steroid refractory as per institutional criteria or per physician decision in case institutional criteria were not available and were permitted to have received additional prior systemic treatment for chronic GvHD in addition to corticosteroids. Patients were considered treatment naïve if they had not received any prior systemic treatment for chronic GvHD (except for a maximum 72 hours prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of chronic GvHD). In addition to Jakavi, patients continued use of systemic corticosteroids and/or CNI (cyclosporine or tacrolimus) and topical corticosteroid therapies were also allowed per institutional guidelines. In REACH5, 23 patients (51.1%) received concomitant CNIs. Patients could also have received standard allogeneic stem cell transplantation supportive care including anti-infective medicinal products and transfusion support. Jakavi was to be discontinued in case of lack of response to chronic GvHD treatment day 169.
Tapering of Jakavi was allowed after the day 169 visit.
Male and female patients accounted for 64.4% (n=29) and for 35.6% (n=16) of patients, respectively, with 30 patients (66.7%) with pre-transplant disease history of underlying malignancy, most frequently leukaemia (27 patients, 60%).
Among the 45 paediatric patients enrolled in REACH5, 17 (37.8%) were treatment-naïve chronic GvHD patients and 28 (62.2%) were SR chronic GvHD patients. The disease was severe in 62.2% of patients and moderate in 37.8% of patients. Thirty-one (68.9%) patients had skin involvement, eighteen (40%) had mouth involvement, and fourteen (31.1%) had lung involvement.
The ORR at day 169 (primary efficacy endpoint) was 40% (90% CI: 27.7, 53.3) in all REACH5 paediatric patients, and 39.3% in SR patients.
Ruxolitinib is a Biopharmaceutical Classification System (BCS) class 1 compound, with high permeability, high solubility and rapid dissolution characteristics. In clinical studies, ruxolitinib is rapidly absorbed after oral administration with maximal plasma concentration (Cmax) achieved approximately 1 hour post-dose. Based on a human mass balance study, oral absorption of ruxolitinib, as ruxolitinib or metabolites formed under first-pass, is 95% or greater. Mean ruxolitinib Cmax and total exposure (AUC) increased proportionally over a single dose range of 5 to 200 mg. There was no clinically relevant change in the pharmacokinetics of ruxolitinib upon administration with a high-fat meal. The mean Cmax was moderately decreased (24%) while the mean AUC was nearly unchanged (4% increase) on dosing with a high-fat meal.
The mean volume of distribution at steady state is approximately 67.5 litres in adolescent and adult acute GvHD patients and 60.9 litres in adolescent and adult chronic GvHD patients. The mean volume of distribution at steady state is approximately 30 litres in paediatric patients with acute or chronic GvHD and with a body surface area (BSA) below 1 m². At clinically relevant concentrations of ruxolitinib, binding to plasma proteins in vitro is approximately 97%, mostly to albumin. A whole body autoradiography study in rats has shown that ruxolitinib does not penetrate the blood-brain barrier.
Ruxolitinib is mainly metabolised by CYP3A4 (>50%), with additional contribution from CYP2C9. Parent compound is the predominant entity in human plasma, representing approximately 60% of the drug-related material in circulation. Two major and active metabolites are present in plasma representing 25% and 11% of parent AUC. These metabolites have one half to one fifth of the parent JAK-related pharmacological activity. The sum total of all active metabolites contributes to 18% of the overall pharmacodynamics of ruxolitinib. At clinically relevant concentrations, ruxolitinib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 and is not a potent inducer of CYP1A2, CYP2B6 or CYP3A4 based on in vitro studies. In vitro data indicate that ruxolitinib may inhibit P-gp and BCRP.
Ruxolitinib is mainly eliminated through metabolism. The mean elimination half-life of ruxolitinib is approximately 3 hours. Following a single oral dose of [14C]-labelled ruxolitinib in healthy adult subjects, elimination was predominately through metabolism, with 74% of radioactivity excreted in urine and 22% via faeces. Unchanged parent substance accounted for less than 1% of the excreted total radioactivity.
Dose proportionality was demonstrated in the single and multiple dose studies.
Based on studies in healthy subjects, no relevant differences in ruxolitinib pharmacokinetics were observed with regard to gender and race.
No relationship was apparent between oral clearance and gender, patient age or race, based on a population pharmacokinetic evaluation in GvHD patients.
As in adult patients with GvHD, ruxolitinib was rapidly absorbed after oral administration in paediatric patients with GvHD. Dosing in children between 6 and 11 years old at 5 mg twice daily achieved comparable exposure to a dose of 10 mg twice daily in adolescents and adults with acute and chronic GvHD, confirming the exposure matching approach implemented as part of the extrapolation assumption. In children between 2 and 5 years old with acute and chronic GvHD, the exposure matching approach suggested a dose of 8 mg/m² twice daily.
Ruxolitinib has not been evaluated in paediatric patients with acute or chronic GvHD below the age of 2 years, therefore modelling which accounts for age-related aspects in younger patients has been used to predict the exposure in these patients, based on the data from adult patients.
Based on a pooled population pharmacokinetic analysis in paediatric patients with acute or chronic GvHD, clearance of ruxolitinib decreased with decreasing BSA. Clearance was 10.4 l/h in adolescent and adult patients with acute GvHD and 7.8 l/h in adolescent and adult patients with chronic GvHD, with a 49% intersubject variability. In paediatric patients with acute or chronic GvHD and with a BSA below 1 m², clearance was between 6.5 and 7 l/h. After correcting for the BSA effect, other demographic factors such as age, body weight and body mass index did not have clinically significant effects on the exposure of ruxolitinib.
Renal function was determined using both Modification of Diet in Renal Disease (MDRD) and urinary creatinine. Following a single ruxolitinib dose of 25 mg, the exposure of ruxolitinib was similar in subjects with various degrees of renal impairment and in those with normal renal function. However, plasma AUC values of ruxolitinib metabolites tended to increase with increasing severity of renal impairment, and were most markedly increased in the subjects with severe renal impairment. It is unknown whether the increased metabolite exposure is of safety concern. A dose modification is recommended in patients with severe renal impairment.
Following a single ruxolitinib dose of 25 mg in patients with varying degrees of hepatic impairment, the mean AUC for ruxolitinib was increased in patients with mild, moderate and severe hepatic impairment by 87%, 28% and 65%, respectively, compared to patients with normal hepatic function. There was no clear relationship between AUC and the degree of hepatic impairment based on Child-Pugh scores. The terminal elimination half-life was prolonged in patients with hepatic impairment compared to healthy controls (4.1 to 5.0 hours versus 2.8 hours). A dose reduction of approximately 50% is recommended for MF and PV patients with hepatic impairment (see section 4.2).
In GvHD patients with hepatic impairment not related to GvHD, the starting dose of ruxolitinib should be reduced by 50%.
Ruxolitinib has been evaluated in safety pharmacology, repeated dose toxicity, genotoxicity and reproductive toxicity studies and in a carcinogenicity study. Target organs associated with the pharmacological action of ruxolitinib in repeated dose studies include bone marrow, peripheral blood and lymphoid tissues. Infections generally associated with immunosuppression were noted in dogs. Adverse decreases in blood pressure along with increases in heart rate were noted in a dog telemetry study, and an adverse decrease in minute volume was noted in a respiratory study in rats. The margins (based on unbound Cmax) at the non-adverse level in the dog and rat studies were 15.7-fold and 10.4-fold greater, respectively, than the maximum human recommended dose of 25 mg twice daily. No effects were noted in an evaluation of the neuropharmacological effects of ruxolitinib.
In juvenile rat studies, administration of ruxolitinib resulted in effects on growth and bone measures. Reduced bone growth was observed at doses ≥5 mg/kg/day when treatment started on postnatal day 7 (comparable to human newborn) and at ≥15 mg/kg/day when treatment started on postnatal days 14 or 21 (comparable to human infant, 1–3 years). Fractures and early termination of rats were observed at doses ≥30 mg/kg/day when treatment was started on postnatal day 7. Based on unbound AUC, the exposure at the NOAEL (no observed adverse effect level) in juvenile rats treated as early as postnatal day 7 was 0.3-fold that of adult patients at 25 mg twice daily, while reduced bone growth and fractures occurred at exposures that were 1.5- and 13-fold that of adult patients at 25 mg twice daily, respectively. The effects were generally more severe when administration was initiated earlier in the postnatal period. Other than bone development, the effects of ruxolitinib in juvenile rats were similar to those in adult rats. Juvenile rats are more sensitive than adult rats to ruxolitinib toxicity.
Ruxolitinib decreased foetal weight and increased post-implantation loss in animal studies. There was no evidence of a teratogenic effect in rats and rabbits. However, the exposure margins compared to the highest clinical dose were low and the results are therefore of limited relevance for humans. No effects were noted on fertility. In a pre- and post-natal development study, a slightly prolonged gestation period, reduced number of implantation sites, and reduced number of pups delivered were observed. In the pups, decreased mean initial body weights and short period of decreased mean body weight gain were observed. In lactating rats, ruxolitinib and/or its metabolites were excreted into the milk with a concentration that was 13-fold higher than the maternal plasma concentration. Ruxolitinib was not mutagenic or clastogenic. Ruxolitinib was not carcinogenic in the Tg.rasH2 transgenic mouse model.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.