30 Refractory cutaneous lupus: use of thalidomide or lenalidomide for refractory lupus skin disease

Abstract

<h3></h3> Cutaneous lupus erythematosus (CLE) may cause extensive skin damage leading to aesthetic prejudice and poor quality of life. Antimalarial agents are recommended as first-line systemic therapy for CLE patients with moderate-to-severe skin lesions. In case of failure of antimalarial agents, a European expert consensus for CLE treatment and EULAR recommendation for systemic lupus erythematosus (SLE) recommend adding quinacrine, methotrexate, retinoids, dapsone or mycophenolate mofetil.¹ However, the overall efficacy of these second-line treatments is approximately 50% depending on CLE subtypes and may be associated with potential toxicity. Thalidomide (a-N-phthalimidoglutarimide) is currently recommended as a ‘rescue’ therapy in patients with severe and refractory CLE treatment. However, in France, a ‘Temporary Recommendations for Use’ has been granted for thalidomide in CLE after failure of antimalarials as second-line agent.^{1 2} Moreover, in a systematic literature review including 21 observational studies and 548 patients the pooled rate of response to thalidomide 50–100mg/day was 90% (95% CI, 85–94), with similar response rates between CLE subtypes.³ The clinical benefits need to be balanced against potential adverse events with a pooled rate of thalidomide withdrawal related to adverse events of 24% (95% CI 14–35) including high teratogenicity, peripheral neuropathy 16% (95% CI 9–25), thromboembolic events in 2% (95% CI 1–3). Moreover, the efficacy of thalidomide is only suppressive with a rate of relapse of 71% (95% CI 65–77) after thalidomide withdrawal which supports the use of a minimal maintenance dose.³ In case of failure of thalidomide, lenalidomide 5 mg/day a 4-amino-glutamyl analogue of thalidomide has shown promising results with partial response of 88% in a retrospective study of 40 patients.⁴ Importantly, no cases of new or worsening peripheral thalidomide-induced neuropathy was reported with lenalidomide.⁴ A case of progression to SLE with renal involvement was reported in a patient with isolated CLE after starting lenalidomide.⁵ Recent data did not confirm this finding but suggested that lenalidomide has little or no effect on global SLE activity. <h3>Learning Objectives</h3> Describe the therapeutic strategy in CLE Explain when to prescribe thalidomide and lenalidomide Discuss the safety profile of thalidomide and lenalidomide <h3>References</h3> Fanouriakis A, Kostopoulou M, Alunno A, <i>et al</i>. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. <i>Ann Rheum Dis</i>. 2019;<b>78</b>(6):736–45. Kuhn A, Aberer E, Bata-Csörgő Z, <i>et al</i>. S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). <i>J Eur Acad Dermatol Venereol</i>. 2017;<b>31</b>(3):389–404. Chasset F, Tounsi T, Cesbron E, <i>et al</i>. Efficacy and tolerance profile of thalidomide in cutaneous lupus erythematosus: A systematic review and meta-analysis. <i>J Am Acad Dermatol</i>. 2018;<b>78</b>(2):342–50.e4. Aitmehdi R, Arnaud L, Francès C, <i>et al</i>. Long-term efficacy and safety outcomes of lenalidomide for cutaneous lupus erythematosus: a multicenter retrospective observational study of 40 patients. <i>J Am Acad Dermatol</i>. 2020. Braunstein I, Goodman NG, Rosenbach M, <i>et al</i>. Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: histologic and circulating leukocyte profile and potential risk of a systemic lupus flare. <i>J Am Acad Dermatol</i>. 2012;<b>66</b>(4):571–82.