BREVACTA Study: Long-term Efficacy and Safety of Subcutaneous Tocilizumab Every 2 Weeks in RA Patients with Inadequate Response to DMARDs

20 Jul, 21

Introduction

Tocilizumab (TCZ) -IV has well-established efficacy and a manageable safety profile, both as monotherapy or in combination with disease-modifying antirheumatic drugs (DMARD), in patients with rheumatoid arthritis (RA). The safety and efficacy of TCZ-SC are comparable with TCZ-IV as monotherapy and with DMARD, and TCZ-SC has been approved for use globally.

Aim

To evaluate the long-term efficacy and safety of subcutaneous tocilizumab (TCZ-SC) every 2 weeks (q2w) over 2 years in patients with rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARD).

Patient Population

Patients with moderate to severe RA who had an inadequate response to ≥ 1 DMARD

Methods

Patients (n = 656) were randomized 2:1 to TCZ-SC 162 mg q2w or placebo-SC q2w plus DMARD
After a 24-week double-blind period, patients (n = 457) were rerandomized to open-label
TCZ-SC q2w by means of prefilled syringe or autoinjector
Escape therapy with weekly TCZ-SC was available for patients with inadequate efficacy from week 12
Maintenance of response and safety to 2 years was assessed
Analyses used non-responder imputation

TCZ-SC: subcutaneous tocilizumab; PBO: placebo qw; weekly, WD: withdrew

Outcomes

Evaluations included the percentage of patients who achieved 20%, 50%, and 70% improvements in response per the American College of Rheumatology criteria (ACR20/50/70)
Remission based on the Disease Activity Score using 28 joints calculated with erythrocyte sedimentation rate (DAS28 < 2.6)
Decreases in Health Assessment Questionnaire–Disability Index (HAQ-DI) scores of ≥ 0.30
Radiographic progression from baseline to weeks 24 and 48 was assessed using the modified total Sharp score analysis (mTSS)10 and performed by 2 primary readers, with an adjudicator involved for any discrepancies
Safety assessments included adverse events (AE), laboratory measurements, and immunogenicity

Results

The American College of Rheumatology (ACR) 20 response after TCZ-SC was maintained beyond week 24 and was > 70% at each timepoint
- In PBO–TCZ-SC group, ACR20 response increased from 56% at week 24 to 81% at week 36 and was sustained thereafter through week 96

Figure 1: ACR 20 response in TCZ-SC group and PBO-TCZ-SC group

In the TCZ-SC group
- ACR50/70, 28-joint Disease Activity Score remission, and ≥ 0.30 decrease from baseline in the Health Assessment Questionnaire –Disability Index response rates were also maintained after Week 24 (≥ 50%, > 25%,> 32% and > 56%, respectively)
Efficacy at week 96 measured by ACR 20/50/70 was demonstrated across all weight groups (< 60 kg, 60 to < 100 kg, ≥ 100 kg) with both TCZ-SC and PBO–TCZ-SC arms
Patients in the PBO–TCZ-SC group experienced more radiographic progression at week 48 from baseline than patients in the TCZ-SC

Figure 2: Mean change in mTSS from baseline to weeks 24 and 48

The mean annualized progression rate for mTSS decreased in both treatment arms through Week 48 and was 2-fold higher in the PBO–TCZ-SC arm than in the TCZ-SC arm (0.57 vs 0.29)

Safety

The safety profile of TCZ-SC q2w over 96 weeks was consistent with that in the double-blind period
The rate of AE/100 PY for TCZ-SC q2w did not increase from weeks 24 to 96, and the rate of serious AE (SAE) was low and consistent over time

Analysis in Escape Population

Efficacy

Many patients achieved ACR20 at the end of the study, 35% after escape from TCZ-SC, and 63% from placebo

Figure 3: Efficacy in escape population

The rates of serious adverse events [(11.20/100 patient-years (PY)] including serious infections (3.25/100 PY) were stable through Week 96
No association between anti-TCZ antibody development and loss of efficacy or adverse events was observed

Conclusion

TCZ-SC q2w demonstrated long-term efficacy, including sustained ACR responses, over 96 weeks
The safety profile of TCZ-SC at 96 weeks was comparable with that at 24 weeks
Improvement in efficacy was seen in some patients who did not initially respond to TCZ-SC q2w and who then received TCZ-SC qw

References

J Rheumatol. 2018;45;456-464