AB0956 Leucine-rich alpha-2 glycoproteinis a predictable biomarker for therapeutic response and clinical relapse to biologics, but not to apremilast in patients with psoriasis

Background Leucine-rich alpha-2 glycoprotein (LRG) is a 50 kDa protein produced by hepatocytes, endothelial cells, neutrophils and macrophages, and it was identified as an inflammatory biomarker that correlates with the disease activity of autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis. We recently reported that LRG could also be a biomarker of psoriasis, which correlated with the clinical severity scores such as Psoriais Area and Severity Index (PASI), Disease Activity Score 28 (DAS-28) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) more closely than common inflammation markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The biologics are innovative therapies for psoriasis, however they can cause side effects and increase medical cost. Recently, apremilast, a small molecure inhibitor of phosphodiesterase 4, was approved for treatment of psoriasis in Japan, yet the precise mechanism remains unknown. Objectives To explore the eligibility of serum LRG for a biomarker to monitor the responses to biologics and apremilast in psoriasis. Methods Antibodies to TNF-alpha, IL-12/IL-23p40, IL-17A and IL-17 receptor A and apremilast were administered in patients with psoriasis vulgaris and psoriatic arthritis (n=15, 6, 14, 4 and 8 respectively). Serum LRG levels were measured by enzyme-linked immunosorbent assay. Serum CRP and ESR, and PASI, DAS-28 and BASDAI were also recorded. Results Serum LRG decreased along with the improvement of clinical scores after the administration of biologics, and reflected the change of scores more accurately than CRP and ESR. Furthermore, the LRG levels preceded the changes of clinical symptoms and predicted both primary and secondary treatment failure at the early time point, allowing us to determine if we should increase the doses, discontinue or switch to another drug. In some patients with PASI clear, complete regression of eruption, after biologics, serum LRG rerose from the baseline while their PASI scores remained stable; however, they later relapsed. On the other hand, LRG did not reflect the therapeutic effectiveness of apremilast. Conclusions Serum LRG in psoriasis patients would be a sensitive biomarker for predicting the effectiveness and treatment failure of biologics, but not of apremilast. Monitoring LRG levels may enable us to decide the timing of bio-attenuation and to detect the relapse after discontinuation of biologics. Reference [1] Leucine-rich α-2 glycoprotein is an innovative biomarker for psoriasis. J Dermatol Sci. 2017May;86(2):170–174 Disclosure of Interest Y. Shibata Grant/research support from: AbbVie GK, S. Serada: None declared, M. Fujimoto: None declared, H. Nakajima Grant/research support from: AbbVie GK, S. Sano Grant/research support from: AbbVie GK, T. Naka: None declared