Subjective loss of clinical response to TNFi in axSpA relates to recurrence of MRI bone marrow oedema particularly with long-acting agents

Objectives: Subjective loss of response immediately prior to routine TNFi therapy can occur in axial spondyloarthritis (axSpA). We investigated clinical outcomes in patients taking the first three licenced TNFis and correlated this with recurrence of MRI bone marrow oedema (MRI-BMO).

Methods: Proof-of-concept study including axSpA patients established on etanercept (ETA), adalimumab (ADA) or infliximab (IFX) reporting symptom deterioration prior to next dose. MRI/clinical data were collected prior to scheduled dose (v1), 4 days post-dose (v2) and at the time of patient-reported symptom return (v3). MRI spine/sacroiliac joints utilizing 3 T were scored using the semi-quantitative Leeds MRI scoring system.

Results: A total of 113 clinical assessments and MRIs were performed in 38 participants (ADA = 16, ETA = 12, IFX = 10), mean age 42.1 years ± 24.4(2SD, n = 38), 71.1% male (n = 27/38), 69.7% HLA-B27 positive (n = 23/33). At v1, all patients had high disease activity [ASDAS-CRP = 3 (2.7-3.7)] and 57.9% had MRI-BMO (number of MRI-BMO: ETA = 26, ADA = 59, IFX = 28). Improved clinical responses were seen at v2 [ASDAS-CRP -0.41(-0.81 - 0.30), P =0.018; BASDAI -0.58(-2.2 - 0.52), P =0.024]. Despite just a 4-day interval between v1 and v2, a numerical reduction in MRI-BMO lesions between v1/v2 was observed (ETA = -6, ADA = -10, IFX = -3). By v3, comparatively fewer new BMO lesions were detected in the ETA and ADA groups compared with IFX (ETA = -1, ADA = +3, IFX = +8), although the numbers were too small to enable testing for statistical significance.

Conclusions: Short-lived fluctuations in MRI-BMO were commoner with longer-acting agents and corresponded with subjective loss of clinical response before next scheduled TNFi dose. Larger studies are needed to confirm the possible pathogenic implications of this phenomenon.