The efficacy of hydroxychloroquine on skin involvement in patients with systemic lupus erythematosus: prospective, randomized study

Abstract

Rezumat. Introducere. Afectarea cutanată la pacienţii cu LES, ca şi frecvenţă a implicării organice, este a doua manifestare a lupusului, prezentă la 93% dintre pacienţi pe parcursul evoluţiei bolii. Problema afectărilor cutanate rezidă din potenţialul acestora de a provoca leziuni cutanate ireversibile (cicatrici extinse, alopecie cronică cicatriceală, ulceraţii trenante), de aceea, tratamentul ţintit al acestor pacienţi are importanţă majoră. Conform cunoştinţelor noastre, nu sunt recomandări specifice pentru pacienţii cu LES şi implicare tegumentară, dar se presupune că administrarea hidroxiclorochinei (HCQ) ar avea un rol protectiv in apariţia leziunilor cutanate ireversibile. Reieşind din cele menţionate, am efectuat un studiu prospectiv randomizat pentru a evidenţia eficacitatea hidroxiclorochinei la pacienţii cu LES şi implicare cutanată, prin instrumente clinice validate. Material şi metode. In cercetare au fost incluşi 97 de pacienţi cu LES, conform criteriilor de clasificare SLICC 2012. Subiecţii au fost randomizaţi in două loturi: L0 – tratament de bază nemodificat şi L1 – tratament de bază cu administrarea hidroxiclorochinei. Pacienţii au fost urmăriţi prospectiv timp de 12 luni, in 4 vizite, prin analiza scrorurilor de activitate şi acutizare a LES şi răspunsului cutanat prin CLASI la 3, 6 şi 12 luni. Rezultate. In urma randomizării, s-au format două loturi comparabile: L0 – tratament de bază cu HCQ (51 de pacienţi) şi L1 – tratament de bază fără HCQ (46 de pacienţi). Indicii de activitate SLEDAI şi SELENA au diminuat semnificativ mai mult in L1 versus L0 ([-7,7] vs. [-2,9] pentru SLEDAI şi [-6,6] versus [-5,1] pentru SLAM, respectiv), RR al acutizărilor fiind mai mic in lotul pacienţilor trataţi cu hidroxiclorochină (RR la 6 luni = 0,5; IC95% = 0,25 – 0,98; RR la 12 luni 0,49; IC95% = 0,25 – 0,94). Afectarea cutanată activă, cuantificată prin indicele CLASI, a diminuat in lotul de cercetare cu [-4,8] puncte (p0,05), ambele faţă de debutul tratamentului. Concluzii. Administrarea hidroxiclorochinei, in complex cu tratamentul de bază la pacienţii cu LES şi implicare cutanată, contribuie la diminuarea activităţii bolii şi frecvenţei acutizărilor. Cu referire la afectarea cutanată, hidroxiclorochina contrubuie la regresia leziunilor cutanate active, cuantificate prin indicele CLASI.Abstract. Introduction. Skin involvement in patients with SLE is the second manifestation of lupus, being found in 93% of patients during the course of the disease. Its problem lies on its potential to cause irreversible lesions (extensive scarring, chronic cicatricial alopecia, persisting ulcers), therefore targeted treatment of these patients is important. To our knowledge, there are no specific treatment recommendations for patients with SLE and skin involvement, but it is assumed that hydroxychloroquine (HCQ) administration would have a protective effect in the development of irreversible skin lesions. Based on the foregoing, we conducted a prospective randomized study to highlight the effectiveness of hydroxychloroquine in patients with SLE and cutaneous involvement using validated clinical tools. Material and methods. The research included 97 patients with SLE that fulfilled SLICC, 2012 classification criteria. The subjects were randomized into two groups: L0 − unchanged basic treatment and L1 − basic treatment plus hydroxychloroquine. Patients were followed prospectively for 12 months during four visits: SLE activity, flare scores and skin response by CLASI at 3, 6 and 12 months were assessed. Results. According to randomization, were formed two comparable groups: L0 − basic treatment with HCQ (51 patients) and L1 − basic treatment without HCQ (46 patients). The disease activity by SLEDAI and SLAM decreased more significantly in L1 versus L0 ([-7.7] vs. [-2.9] for SLEDAI and [-6.6] vs. [-5.1] for SLAM, respectively), the RR of flares being lower in the group of patients treated with hydroxychloroquine (RR at 6 months = 0.5, 95%CI = 0.25 to 0.98, RR at 12 months 0.49, 95%CI = 0.25 to 0.94). Active cutaneous involvement, measured by CLASI index, decreased in L1 by [-4.8] points (p0.05), both compared to baseline. Conclusions. The add of the hydroxychloroquine to basic treatment in patients with SLE and skin involvement contributes to the decrease of the disease activity and reduces the frequency of flares. Concerning cutaneous involvement, hydroxychloroquine contributes to the regression of active skin manifestations, as measured by CLASI index