Background/Purpose:

ALX-0061 is a monovalent IL-6R targeting Nanobody, inhibiting signaling via soluble and membrane IL-6R. The safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of ALX-0061 was assessed in a Phase I/II study in patients (pts) with active rheumatoid arthritis (RA) on stable methotrexate (MTX) therapy (1). 
Since remission is the recommended treatment target in the management of RA, the purpose of this post-hoc analysis was to assess induction and maintenance of remission during ALX-0061 treatment.  In addition, the impact of disease remission on physical function following 24-week treatment with ALX-0061 was also assessed.

Methods:

Data were obtained from the multi-center, randomized, double-blind, placebo (PBO) controlled, dose escalation, Phase I/II study (1). During the first 12 weeks (wks) of the multiple ascending dose period, 37 pts received PBO (n=6) or ALX-0061 IV (n=31) at 1 or 3 mg/kg Q4W, or 6 mg/kg Q8W. Patients received stable doses of MTX ranging from 10-25 mg/week. In the second 12 wks period, pts with insufficient EULAR response had the ALX-0061 dose increased or switched from PBO to ALX-0061. 24 pts continued on their originally-assigned ALX-0061 IV dose (8 pts in 1 mg/kg arm, 8 pts in 3 mg/kg arm, and 8 pts in 6 mg/kg arm), 4 pts changed their dosing regimen, and 3 pts switched from PBO to ALX-0061. This post-hoc analysis utilized data from pts whose originally assigned ALX-0061 dose remained unmodified. Clinical remission as defined by both DAS28<2.6 and the ACR/EULAR Boolean-based definition was evaluated at the time points 12, 16, 20, and 24 wks. Patient functional status was assessed using the Health Assessment Questionnaire (HAQ) with HAQ < 0.5 defining normal physical function. An improvement in HAQ score > 0.25 was considered to be clinically meaningful.

Results:

At week 24, 62.5% (15/24) of pts treated with ALX-0061 achieved DAS28<2.6 remission, while remission using the more stringent Boolean criteria was observed in 29.2% (7/24) of the pts. Looking at maintenance of remission between 12 and 24 wks, approximately one third, i.e. 37.5% and 29.2%, of pts treated with ALX-0061 remained in DAS28 remission during the last 3 (at wks 16, 20, and 24) and 4 (at wks 12, 16, 20, and 24) consecutive time points, respectively. Maintenance of remission based on the Boolean criteria was also observed, being 20.8 and 16.7% of the pts for up to the last 3 or 4 successive time points. At week 24, clinically meaningful improvement in HAQ was observed in 66.7% (16/24) of the pts treated with ALX-0061. Compared to pts not in remission, more pts in DAS28 remission at week 24 achieved normal physical function (86.7% vs. 22.2%). Moreover, normal physical function was observed in 100% (7/7) of pts in Boolean remission at week 24. 

Conclusion:

In this study in pts with established RA, ALX-0061 induced and maintained remission as assessed by both DAS28 and the more stringent Boolean remission definition. Control of disease activity was also important in regaining normal physical function, supporting treat-to-target management of RA as reflected in the EULAR recommendations.

Reference:(1) Ann Rheum Dis 2013;72(Suppl3):64

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-clinical-remission-on-physical-function-in-patients-with-rheumatoid-arthritis-treated-with-alx-0061-post-hoc-analysis-of-phase-iii-data/