Hydroxychloroquine for the Treatment of Immune Thrombocytopenia Associated with Antinuclear Antibody in Patients Refractory to First-Line treatments .

Although, corticosteroids (CS) are commonly used as the first-line treatment for lupus-associated immune thrombocytopenia (ITP), few patients fail to respond to CS and a majority of the responders relapse when CS are withdrawn. Hydroxychloroquine (HCQ) is commonly used in both cutaneous and systemic lupus due to its immunomodulatory properties. In a previous report on lupus-associated immune thrombocytopenia (ITP), it has been suggested that HCQ could have an effect on the platelet count in this setting (Arnal C et al. J Rheumatol 2002). The objective of the study was to better assess the efficacy of HCQ as a treatment of ITP associated with positive antnuclear antibody (ANA) in patients who failed to achieve a durable response after a first-line treatment.

This single centre retrospective study was conducted at the French national referral center for adult's immune cytopenias. To be included in the study, all patients had to fulfil the following criteria: 1) Definite diagnosis of ITP with a platelet count < 50 × 10⁹/l at diagnosis 2) Positive ANA at a significant titer (i.e ≥ 1/160 on Hep2 cells), with or without a definite diagnosis of systemic lupus erythematosus (SLE) according to the ACR-revised criteria and 3) No response or incomplete response to at least one previous treatment-line. Response to HCQ was considered when the platelet count was persistently (at least for 3 consecutive months) maintained above 150×10⁹/l (complete response: CR), and when the platelet count increased and persisted above 30 × 10⁹/l with at least a doubling of the baseline count (partial response: PR).

The data from 40 patients (32 F, 8 M) with a median age of 35 yrs (range: 15-75) were analyzed. The median platelet count at ITP diagnosis was 13×10⁹/l (range: 1-46). Twelve (30%) patients had a SLE-associated ITP (4 or more SLE ACR-criteria) whereas 28 patients (70%) had positive ANA without definite SLE. The median HCQ dose was 200 mg bid (200 to 600 mg/d) and the median time between ANA-associated-ITP diagnosis and HCQ first administration was 4 months (range: 1-120). HCQ was given after failure of a median of 2 treatment-lines [1 to 5 including oral prednisone (n=39), IVIg (n=15), danazol (n=5), dapsone (n=2), splenectomy (n=2), anti-D (n=1) and immunosuppressive agents (n=2)]. HCQ was given in combination with other treatments in 36 patients (90%) including oral prednisone (n=36) (median initial dose: 50 mg/day, range: 30 to 65 mg/day), dapsone (n=8), danazol (n=5). The median duration of HCQ treatment was 5 years (range: 0.4 to 12 yrs).

The overall response rate for was 60% (24/40), with 18 CR and 6 PR. All the responses were sustained with a median follow-up of 64 months (range: 6 to 146 mths). At the end of the follow-up period, all concomitant therapies could be either stopped (n = 29 patients) or tapered [n = 7 patient left on low dose of prednisone (less than 10 mg/d)].

The response rate was significantly higher in the SLE group (83%; 10/12) when compared to the ANA-positive group (50%; 14/28) (p <0.05). The overall safety of HCQ was good and none of the patients stopped the treatment because of a side-effect. Blood HCQ concentration was checked in 2 non-responding patients and was found below therapeutic range in both cases.

This retrospective study strongly suggests that HCQ is a safe, and effective treatment for ITP patients with high titer of ANA who failed to achieve a lasting response after a first-line treatment and mainly after CS. HCQ appears particularly attractive in the subgroup of patients who fulfil the SLE ACR-revised criteria. This costless treatment should therefore be systematically considered in this setting regardless SLE-activity. Moreover, it is likely that HCQ may also be helpful as a corticosteroid-sparing strategy in patients with chronic ITP and positive ANA but this observation needs further confirmation throughout a prospective analysis.

No relevant conflicts of interest to declare.