The mean change from baseline CPK over time was observed in the baricitinib 2 mg and baricitinib 4 mg groups for the 16-week placebo controlled dataset, presented in Mean Change From Baseline CPK in 16-Weeks in Placebo-Controlled Atopic Dermatitis Clinical Trials, and extended baricitinib dataset (previous data cut, N=2531; patient-years of exposure [PYE]=2247; median duration 310 days), presented in Mean Changes in CPK Over Time in Patients Treated With BARI 4 mg and BARI 2 mg in the Extended Dataset in the Atopic Dermatitis Clinical Trials.

The integrated datasets used to evaluate changes in CPK are described in more detail in Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials.

Increase in serum CPK to at least grade 1 was the most common laboratory change and was recorded for 19.3% and 23.8% of patients in the 2-mg and 4-mg groups, respectively, vs 10.3% in the placebo group; frequencies were also higher for baricitinib groups vs placebo for CPK increases to at least Grades 2 and 3.2 A summary of CTCAE grade increases for each dataset is provided in Overview of CTCAE Grade Increase in CPK in Atopic Dermatitis Clinical Trials.

A post hoc analysis was performed in patients with a CPK >5 x ULN (grade 3 or grade 4) at any point in the All BARI AD dataset. There were initially 95 patients identified, but one patient was excluded from the post hoc analysis as this patient’s CPK was elevated on day one of the study prior to taking BARI.1

Of the 94 patients identified, baseline characteristics included

• mean age: 31 years
• males: 74%
• dose received: BARI 4-mg (39%), 2-mg (45%), or 1-mg (16%), and
• race: Caucasian (39%), Asian (32%), Caucasian-Hispanic-Latino (18%), African American (6%), Multiple (4%), and Unknown (1%).1
  

Of the 94 patients with a CPK >5 × ULN (grade 3 or grade 4)

• 75.5% had a normal baseline CPK
• a mean maximum CPK of 5556 U/L, median CPK 2779 U/L, and maximum CPK value of 28540 U/L, and
• 82% reported strenuous exercise or work.1

The time to onset of CPK >5 x ULN (grade 3 or 4) was a mean of 125 days, a median of 82 days, and a range of 14 to 642 days.

Creatine phosphokinase values returned to baseline in 73% patients, the mean time to return to baseline was 37 days (range of 4 to 126 days).1

Adverse events were reported in 24 patients, and of these

• 12 were mild
• 7 were moderate
• 2 were severe, and
• 3 cases did not have a severity provided.1

Grade 3 or grade 4 CPK (>5 x ULN) elevation led to

• interruption of treatment in 2 (2.1%) patients, and
• discontinuation of treatment in 2 (2.1%) patients.1

In patients with AD who received baricitinib in clinical trials, treatment-emergent (TE) muscle symptoms

• were reported in 43 out of 2636 patients, and
• occurred in 1.6% of patients with an incidence rate of 0.9 per 100 PYE.1

In the All BARI AD dataset, treatment emergent muscle symptoms observed included

• myalgia in 32 (1.2%) patients
• muscle spasms in 10 (0.4%) patients
• muscle tightness in 2 (0.1%) patients
• myofascial pain syndrome in 1 (<0.1%) patient, and
• myositis in 1 (<0.1%) patient.1

There were no confirmed cases of rhabdomyolysis.1,3