Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Jakafi was assessed in 617 patients in six clinical studies with a median duration of follow-up of 10.9 months, including 301 patients with MF in two Phase 3 studies.

In these two Phase 3 studies, patients had a median duration of exposure to Jakafi of 9.5 months (range 0.5 to 17 months), with 89% of patients treated for more than 6 months and 25% treated for more than 12 months. One hundred and eleven (111) patients started treatment at 15 mg twice daily and 190 patients started at 20 mg twice daily. In patients starting treatment with 15 mg twice daily (pretreatment platelet counts of 100 to 200 x 10

In a double-blind, randomized, placebo-controlled study of Jakafi, among the 155 patients treated with Jakafi, the most frequent adverse reactions were thrombocytopenia and anemia

Discontinuation for adverse events, regardless of causality, was observed in 11% of patients treated with Jakafi and 11% of patients treated with placebo.

Table 12 presents the most common nonhematologic adverse reactions occurring in patients who received Jakafi in the double-blind, placebo-controlled study during randomized treatment.

In the two Phase 3 clinical studies, median time to onset of first CTCAE Grade 2 or higher anemia was approximately 6 weeks. One patient (< 1%) discontinued treatment because of anemia. In patients receiving Jakafi, mean decreases in hemoglobin reached a nadir of approximately 1.5 to 2.0 g/dL below baseline after 8 to 12 weeks of therapy and then gradually recovered to reach a new steady state that was approximately 1.0 g/dL below baseline. This pattern was observed in patients regardless of whether they had received transfusions during therapy.

In the randomized, placebo-controlled study, 60% of patients treated with Jakafi and 38% of patients receiving placebo received red blood cell transfusions during randomized treatment. Among transfused patients, the median number of units transfused per month was 1.2 in patients treated with Jakafi and 1.7 in placebo treated patients.

In the two Phase 3 clinical studies, in patients who developed Grade 3 or 4 thrombocytopenia, the median time to onset was approximately 8 weeks. Thrombocytopenia was generally reversible with dose reduction or dose interruption. The median time to recovery of platelet counts above 50 x 10

In the two Phase 3 clinical studies, 1% of patients reduced or stopped Jakafi because of neutropenia.

Table 13 provides the frequency and severity of clinical hematology abnormalities reported for patients receiving treatment with Jakafi or placebo in the placebo-controlled study.

In a randomized, open-label, active-controlled study, 110 patients with PV resistant to or intolerant of hydroxyurea received Jakafi and 111 patients received best available therapy 

Clinically relevant laboratory abnormalities are shown in Table 15.

In a single-arm, open-label study, 71 adults (ages 18-73 years) were treated with Jakafi for aGVHD failing treatment with steroids with or without other immunosuppressive drugs 

There were no fatal adverse reactions to Jakafi. An adverse reaction resulting in treatment discontinuation occurred in 31% of patients. The most common adverse reaction leading to treatment discontinuation was infection (10%). Table 16 shows the adverse reactions other than laboratory abnormalities.

Selected laboratory abnormalities during treatment with Jakafi are shown in Table 17.

In a Phase 3, randomized, open-label, multi-center study, 165 patients were treated with Jakafi and 158 patients were treated with best available therapy for cGVHD failing treatment with steroids with or without other immunosuppressive drugs

There were five fatal adverse reactions to Jakafi, including 1 from toxic epidermal necrolysis and 4 from neutropenia, anemia and/or thrombocytopenia. An adverse reaction resulting in treatment discontinuation occurred in 18% of patients treated with Jakafi. An adverse reaction resulting in dose modification occurred in 27%, and an adverse reaction resulting in treatment interruption occurred in 23%. The most common hematologic adverse reactions (incidence > 35%) are anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥ 20%) are infections (pathogen not specified) and viral infection.

Table 18 presents the most frequent nonlaboratory adverse reactions occurring up to Cycle 7 Day 1 of randomized treatment.

Clinically relevant laboratory abnormalities are shown in Table 19.

The following adverse reactions have been identified during post-approval use of Jakafi. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: