Adalimumab Treatment Demonstrates Long-term Safety Profile in Japanese Patients with RA

Introduction

Adalimumab (ADA) is a fully human anti- tumour necrosis factor (TNF) monoclonal antibody that reduces the inflammatory response in patients with rheumatoid arthritis (RA) by binding specifically to TNF, thereby blocking its interaction with TNF receptors on the surfaces of cells.

Aim

To evaluate the long-term (up to 3 years) incidence of adverse drug reactions (ADRs), including infections, serious infections, and malignancies, in the clinical setting, and to identify factors associated with the safety and effectiveness of ADA (adalimumab) in patients with rheumatoid arthritis (RA)

Patient Profile

• Five hundred and fifty-two patients who completed the previous all-case PMS for 6 months and fulfilled following conditions
  • Completion of the Health Assessment Questionnaire (HAQ) or modified Health Assessment Questionnaire (MHAQ) at baseline of the all-case PMS
  • Had been prescribed ADA in accordance with the Japanese package inserts for the treatment of RA (40 mg administered subcutaneously every other week, increased to 80 mg in case of insufficient efficacy) at the start of the long-term study
  • Using ADA continuously for 6 months during the all-case PMS
  • Free of malignancy or history of malignancy at baseline of the all-case PMS
  • Had evaluable disease activity as assessed using the DAS28

Methods

• Multi-center, single-cohort, observational study
• Safety analysis set included  509 patients , of these patients, 430 were included in the effectiveness analysis set
• Patients were followed for 3 years after the start of treatment
• Every 6 months information on safety and effectiveness was collected using an electronic data capture system or paper case report forms
• The data obtained during the 3 years after the initiation of ADA treatment, including the first 6-month period of the all-case PMS, were analyzed

Endpoints

• Primary Endpoint
  •  Occurrence of ADRs, including malignancy and infection
• Secondary Endpoints
  • Risk factors for the development of ADRs
  • Serious ADRs (SADRs)
  • Serious infections during long-term treatment of RA with ADA
  • Predictive factors for remission using the 28-joint count Disease Activity Score based on 4 erythrocyte sedimentation rates (DAS28-4/ESR)

Results

Safety

• The 3 year observation showed  292 Adverse drug reactions (ADRs) were reported in 34.2% of patients (23.3/100 person-years [PYs])
• Serious ADRs (SADRs) were reported in 10.6% (5.9/100 PYs)
• The most common ADRs and SADRs were infection (16.5%) and serious infection (6.1%), respectively

• Eight malignancies were observed in seven patients (1.4%); however, no patients developed malignant lymphoma

• Multivariate analysis revealed that the risk factors for SADRs were age > 65 years and respiratory disorder at baseline

Effectiveness

• The proportion of patients who achieved remission (28-joint count Disease Activity Score based on four erythrocyte sedimentation rates
  • At 36 months, the proportion of patients who achieved remission (DAS28- 4/ESR <2.6) increased over time from 3.3% at baseline to 49.2%, whereas the proportion of patients with high disease activity (DAS28-4/ESR >5.1) decreased from 51.9% at baseline to 1.7% at 36 months
• Significant predictors of failure to achieve DAS28-4/ESR remission were
  • female sex (OR 0.49)
  • age >65 years, (OR 0.59)
  • blood disorders (OR 0.19)
  • advanced Steinbrocker’s stage at baseline (OR, 0.42)

Conclusions

• This observational study reported no unknown safety concerns during the 3-year treatment with ADA in Japanese patients with RA
• Treatment with ADA  was associated with decreased disease activity and increased functional status
• The findings suggest , a special care  be taken when considering the long-term use of ADA in patients with risk factors for ADRs and SADRs
• Physicians need to strike an appropriate balance between the benefits and risks of not only short-term ADA treatment but also long-term treatment

Rheumatology, 28:1, 30-38, DOI: 10.1080/14397595.2017.1304159