Change from baseline of trial endpoints
| T | Day 5–Day 1 | Day 12–Day 1 | ||||
| taVNS median (IQR) | SS median (IQR) | P value | taVNS median (IQR) | SS median (IQR) | P value | |
| Δ VAS pain (0–10 mm) | −5.00 (–5.80 to –3.10) | 0.10 (–10.0 to 1.0) | 0.049 | −5.35 (–5.80 to –1.45) | 0.15 (–0.60 to 0.70) | 0.079 |
| Δ FACIT-F† | 11.00 (4.50 to 16.00) | 0.00 (–2.00 to 1.00) | 0.003 | 12.00 (5.50 to 18.25) | −2.00 (−3.00 to 1.00) | 0.003 |
| % Tender joint reduction | 100.0 (100.0 to 100.0) | 5.27 (-11.1,80.0) | 0.005 | 98.49 (50.0 to 100.0) | 10.00 (0.00 to 34.61) | 0.050 |
| % Swollen joint reduction‡ | 100.0 (100.0 to 100.0) | 9.09 (–8.33 to 57.15) | 0.019 | 100.0 (80.0 to 100.0) | 14.29 (–100.0 to 59.09) | 0.056 |
| Δ PtGA (0–100 mm) | −22.50 (–46.50 to –2.50) | 4.00 (–2.00 to 9.00) | 0.125 | −18.50 (–64.00 to –2.00) | −0.52 (–16.00 to 9.00) | 0.301 |
| Δ PGA (0–3) | −0.51 (−0.99 to –0.30) | 0.04 (–0.06 to 0.12) | 0.053 | −0.50 (−0.84 to –0.08) | 0.03 (0.03 to 0.12) | 0.107 |
| Δ CRP (mg/dL) | 0.00 (–0.23 to 0.00) | 0.05 (-0.10 to 0.15) | 0.165 | 0.00 (–0.20 to 0.00) | -0.05 (–0.23 to 0.08) | 1.000 |
| Δ Serum cytokine | ||||||
| IFNα | 0.00 (0.00 to 0.00) | 0.12 (–0.12 to 1.10) | 0.871 | 0.00 (–0.01 to 0.00) | 0.25 (0.00 to 1.00) | 0.080 |
| IL-1β | −0.01 (–0.40 to 0.20) | −0.01 (–0.02 to 0.02) | 0.820 | −0.01 (–0.04 to 0.00) | −0.04 (–0.05 to 0.04) | 0.874 |
| IL-8 | −0.21 (−2.25 to –0.01) | 0.77 (–1.10 to 1.80) | 0.144 | −0. 17 (–2.54 to 0.45) | −0. 20 (–2.80 to 0.10) | 0.963 |
| IL-10 | 0.05 (–0.10 to 1.10) | −0.08 (–0.16 to 0.30) | 0.600 | 0.12 (–0.17 to 0.23) | 0.04 (–0.10 to 0.40) | 0.569 |
| TNF | −0.05 (–0.25 to 0.12) | 0.00 (–0.80 to 0.20) | 0.943 | −0.05 (–0.25,0.12) | −0.05 (–0.20 to 0.20) | 0.848 |
| Il-6 | −0.39 (−2.89 to –0.03) | 0.17 (–3.35 to 2.6) | 0.112 | −0.17 (–3.13 to 0.67) | −0.20 (–3.35 to 0.25) | 0.960 |
| IL1-RA | −0.06 (–1.73 to 0.66) | 2.92 (–2.63 to 10.30) | 0.603 | 0.41 (–10.68 to 1.73) | −0.39 (–2.73 to 2.32) | 0.741 |
| Il-18 | 0.71 (–0.23 to 8.20) | −0.21 (–2.47 to 0.92) | 0.208 | −0.55 (–2.98 to 0.48) | 0.10 (–9.37 to 1.21) | 0.603 |
| Δ Plasma neuropeptide | ||||||
| Substance P | −2.76 (–4.79 to 0.94) | 0.09 (–5.57 to 4.48) | 0.008 | 4.90 (–2.41 to 8.23) | 5.08 (0.24 to 9.98) | 0.335 |
| Neuropeptide Y | −0.80 (–7.43 to 2.28) | −2.25 (–4.38 to 5.48) | 0.509 | 0.30 (–6.05 to 5.20) | 2.0 (–1.38 to 14.98) | 0.242 |
| CGRP | 0.0 (–2.0 to 4.7) | 0.0 (–1.98 to 2.40) | 0.960 | −0.7 (–17.15 to 0.83) | 0.0 (–1.68 to 0.99) | 0.484 |
| Δ Kynurenine pathway | ||||||
| Kynurenine | −0.02 (–0.35 to 0.18) | 0.155 (–0.06 to 0.51) | 0.121 | −0.17 (–0.56 to 0.18) | −0.27 (–0.01 to 0.65) | 0.055 |
| Quinolinic acid | −51.0 (–99.5 to –14.75) | −35 (−173.5 to 28.75) | 0.674 | −100.0 (−138 to –41.75) | −12.5 (–74.75 to 62.0) | 0.121 |
| Kynurenine/tryptophan | 0.001 (–0.004 to 0.005) | −0.002 (–0.011 to 0.010) | 0.603 | −0.003 (–0.007 to 0.008) | 0.001 (–0.004 to 0.008) | 0.603 |
*Negative scores correspond to a reduction in the measured endpoint from baseline.
†Higher FACIT-F scores correspond to lower fatigue.
‡Data shown for seven taVNS and five SS subjects with swollen joints at baseline.
CGRP, calcitonin gene-related peptide ; CRP, C-reactive protein; IFNα, interferon alpha; IL, interleukin; IL1-RA, interleukin-1 receptor antagonist; PGA, Physician Global Assessment ; PtGA, Patient Global Assessment of disease activity ; SS, sham stimulation ; taVNS, transcutaneous auricular vagus nerve stimulation; TNF, tumour necrosis factor; VAS, Visual Analogue Scale.