The risk of malignancies including lymphoma is increased in patients with rheumatoid arthritis. Immunomodulatory medicinal products may increase the risk of malignancies including lymphoma. The clinical data are insufficient to assess the potential incidence of malignancies following exposure to baricitinib. Long-term safety evaluations are ongoing.1

Patients with a history of malignancy were not uniformly excluded from the BARI phase 3 clinical development program.2

Patients who were able to participate in the BARI phase 3 clinical trials included patients with

• cervical carcinoma in situ that had been resected with no evidence of recurrence or metastatic disease for at least 3 years, and
• basal cell or squamous epithelial skin cancers that had been completely resected with no evidence of recurrence for at least 3 years.2

However, patients were excluded from the phase 3 trials if they had

• a history of lymphoproliferative disease
• signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly
• active primary or recurrent malignant disease, or
• been in remission from clinically significant malignancy for <5 years.2

Each of the 4 phase 3 studies in the clinical program evaluated a distinct treatment population of patients with moderate-to-severe RA.

• RA-BEGIN compared BARI 4 mg monotherapy, BARI 4 mg plus MTX, and MTX monotherapy in patients who had limited or no prior treatment with MTX and were naïve to other DMARDs.3
• RA-BEAM compared BARI 4 mg vs placebo or adalimumab, with background MTX, in patients with inadequate response to MTX.4 
  
• RA-BUILD compared BARI 2 mg and 4 mg vs placebo, with background csDMARD therapy, in patients with inadequate response to csDMARDs.5
• RA-BEACON compared BARI 2 mg and 4 mg vs placebo, with background csDMARD therapy, in patients with an inadequate response to at least one TNF inhibitor, who may also have had an inadequate response to one or more non-TNF inhibitor biologic DMARDs.6

Medical history, including malignancy, was recorded upon enrollment into each of the BARI phase 3 clinical studies.

A history of malignancy was defined as malignancy that was previously diagnosed and resolved prior to study entry.

As shown in Comorbid Conditions of Special Interest in the Baricitinib Phase 3 Studies, the number of patients who had a historical diagnosis of malignancy at baseline included

• 1.8% (12/684) in RA-BUILD
• 2.1% (11/527) in RA-BEACON
• 1.3% (17/1305) in RA-BEAM, and
• 2.2% (13/584) in RA-BEGIN.2

A preexisting malignancy was defined as malignancy that was previously diagnosed and was ongoing at study entry.2

In RA-BEGIN, 1 patient (0.2%) in the MTX treatment group reported preexisting malignant tumors and skin neoplasms at enrollment Comorbid Conditions of Special Interest in the Baricitinib Phase 3 Studies.2

The individual phase 3 clinical trials were not designed to detect differences in the efficacy and safety of BARI for the treatment of moderate to severe RA in patients with or without a medical history or pre-existing condition of malignancy. Due to the small numbers of patients with a medical history or preexisting condition of malignancy in the BARI phase 3 clinical program for RA, an analysis of the efficacy and safety of BARI in these patients is not feasible.

BARI = baricitinib

csDMARD = conventional synthetic disease-modifying antirheumatic drug

DMARD = disease-modifying antirheumatic drug

MTX = methotrexate

PBO = placebo

RA = rheumatoid arthritis

TNF = tumor necrosis factor

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.