Background/Purpose:

Rheumatoid arthritis (RA) is associated with significant pain and loss of physical function. We evaluated self-reported pain and physical function in adults patients with moderate-severe, active RA treated with mavrilimumab in combination with MTX in a 3-mo phase 2a, double-blind, placebo-controlled, ascending dose study.

Methods:

Eligible patients had moderate-severe RA (DAS28-CRP ≥3.2) of ≥3 mos duration, were DMARD-IR on stable MTX (7.5–25 mg/wk), and positive for auto-antibodies ACPA and/or RF. 192 and 92 patients were randomized to subcutaneous mavrilimumab (10–100mg) and placebo, respectively, given every other wk for 12 wks. The primary endpoint was proportion of patients achieving a ≥1.2 decrease from baseline in DAS28-CRP at wk 12. Pain visual analog scale (VAS) and Short Form-36 physical component summary (SF-36 PCS) score were used to assess pain and physical function. The proportion of responders using minimal clinically important differences was assessed. In a post-hoc analysis, relationships between pain, physical function, and DAS28-CRP were examined using linear regression.

Results:

At its highest dose, mavrilimumab 100mg (M100mg) met the primary endpoint vs placebo (difference, 35.5%; p<.001) at wk 12. In addition, following a single dose at wk 2, M100mg demonstrated a statistically significant improvement in the proportion of pain responders compared to placebo (difference, 16.7%; p=.034). This improvement was maintained until 4 wks after the last dose at wk 16 (difference, 24.7%; p=.007). At the first assessment of physical function (SF-36 PCS) at wk 4, M100mg demonstrated a statistically significant improvement in the response rate compared to placebo (difference, 26.7%; p=.004) (Table). This improvement was maintained to the final assessment at wk 12. The relationship between improvements in pain, physical function, and DAS28-CRP showed that, on average, a patient achieving a minimally important improvement in pain following 12 wks of M100mg also had an improvement of 5.71 (95% CI 4.04, 7.38) in the SF-36 PCS and 1.66 (95% CI -1.91, -1.41) in the DAS28-CRP score. Lower doses of mavrilimumab (10mg, 30mg, and 50mg) generally did not yield statistically significant improvements over placebo for these 3 endpoints, except for 30mg (n=49) in DAS28-CRP as early as wk 6 (difference, 25.2%; p=.004). All doses combined (n=192) achieved a response in DAS28-CRP as early as wk 4 (difference, 13.9%; p=.015).

 

Table: Responder Analysis1 (%) of Patient-Reported Outcomes and DAS28-CRP at Wks 4 and 12
‘	Wk 4					Wk 12
	M100mg (N=47)	PBO (N=92)	Difference	95% CI	p-value	M100mg (N=47)	PBO (N=92)	Difference	95% CI	p-value
Pain VAS	46.8	26.1	20.7	3.8, 37.4	0.022	55.3	33.7	21.6	4.2, 38.2	0.018
SF-36 PCS	70.2	43.5	26.7	9.1, 42.7	0.004	70.2	40.2	30.0	12.3, 45.3	0.001
DAS28-CRP2	42.6	17.4	25.2	9.2, 41.3	0.002	68.1	32.6	35.5	17.8, 50.6	<0.001
CI, confidence interval; DAS28-CRP, Disease Activity Score 28 – C-reactive Protein; M100mg, mavrilimumab 100mg; PBO, placebo 1Minimal clinically important difference: VAS, 20mm; SF-36 PCS, 3.1; DAS28-CRP, 1.2 2The mean baseline DAS28-CRP was 5.33 and 5.43 in M100mg and placebo groups, respectively.

Conclusion:

Treatment with mavrilimumab 100mg resulted in an early onset and sustained improvement in pain relief and physical functioning as measured by VAS and SF-36 PCS, respectively, in moderate-severe RA patients. These findings are consistent with improvement in the disease activity (DAS28-CRP) and support further investigation of the blockade of the GM-CSF receptor with mavrilimumab in Phase 2b studies conducted in both DMARD-IR and TNF-IR patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-and-sustained-improvement-in-pain-and-physical-function-as-measured-by-visual-analog-scale-and-short-form-36-physical-component-summary-score-in-rheumatoid-arthritis-patients-treated-with-mavril/