Background/Purpose: Recent studies highlight the usefulness and necessity of biologic agents in the treatment of primary vasculitides. Evidence for the use of biologics in PAN is limited. Objective is to study clinical features and treatment responses of PAN patients needing biologic therapy.

Methods: A retrospective survey of databases from two vasculitis centres (AddenbrookeÕs hospital in the UK & Hacettepe University, Turkey) between 1990-2016 for PAN patients fulfilling the EMEA Vasculitis Classification algorithm was done. Hepatitis B related PAN patients were excluded (n=3). Previous therapies including biologics were recorded. Response to therapy was determined according to the documentation by physicians.

Results: 90 (M/F: 48/42) patients (UK: 45, TR: 45) were included in the study. 16 patients had cutaneous PAN and 12 of the TR patients had a monogenic form of disease (Familial Mediterranean Fever: 7 patients, deficiency of adenosine deaminase 2, DADA2: 5 patients). During a median follow up of 79 (35.5-128) months, 28 patients (31.1%) (8 from TR, 20 from the UK, p = 0.004) were exposed to biologics. Seven of them had more than one biologic. Four of the 16 cutaneous PAN (25%) and 24 of the 74 systemic PAN (32.4%) patients received biologics (p=0.684). Except for one patient with cutaneous PAN, all patients had corticosteroids and cyclophosphamide before biologics.

In patients with cutaneous PAN; RTX was used in two patients (one had good response), CAMPATH in two patients (one with no response), Infliximab (IFX) in one patient (with good response).

RTX and IFX were the most commonly used agents in systemic PAN patients. Complete or partial response was observed in more than half of the patients. Etanercept (ETN) was used in 5 patients; of the 4 patients with DADA2 three responded well, one had partial response and one patient did not respond. Adalimumab was used in two patients but was prematurely stopped in both cases due to serious infection. Interferon alpha was used in two patients and resulted in good response in both. TCZ was used in one patient without any benefit. Distribution of biologics used in patients with systemic PAN is shown in Table.

Response could not be evaluated in 6 patients; due to missing data of two patients, and short duration usage in 4 patients (withdrawal due to adverse effects: 3). Biologics were stopped in four of the patients; due to severe infections in three and anaphylactic reaction in one.

Conclusion: There is an unmet need to establish evidence for biologics in the treatment of PAN as 30 per cent of the patients in this study needed escalation in therapy to biologics. The experiences of RTX and IFX has been mixed with some very good responses and some not responses. Patients with DADA2 responded well to ETN. This probably reflects the fact that PAN is a more heterogeneous condition in terms of genetic background and clinical course.

Table. Distribution of biologics used in patients with systemic PAN

*: Patients with DADA2