Leprosy Mailing List Blog: Ref.: Thalidomide in treating kidney damage

Wednesday, January 8, 2014

Ref.: Thalidomide in treating kidney damage

Leprosy Mailing List – January 8 , 2014

Ref.: Thalidomide in treating kidney damage

From: Steve Walker, LSHTM, London, UK

Dear Dr Schreuder,

I have followed with interest the recent discussion initiated by Dr. Jingquan Wang concerning thalidomide and I think it highlights some important issues faced by clinicians when managing patients with ENL.

1. There remains a lack of evidence on how best to manage this serious complication of leprosy. This was highlighted by a Cochrane review in 2009 (1). In the MDT era there have only been 136 patients randomised in published controlled trials of treatments for ENL (2). The best agents to use to treat ENL, the duration of use, their long-term adverse effects, the benefits and risks of polypharmacy versus single anti-reaction medication all need to be evaluated.

2. Thalidomide is effective for managing many of the features of ENL but how effective is it in ENL associated neuritis or iritis?

3. How should we manage patients with ENL in situations where thalidomide is unavailable or contraindicated?

4. Professor Kar highlighted a case of deep vein thrombosis in one of 17 patients treated with thalidomide and prednisolone. Clinicians should be aware that treatment with thalidomide increases the risk of arterial and venous thromboembloism. This appears to be a class effect as a similar risk association has been reported with lenalidomide. Patients with multiple myeloma (MM) receiving thalidomide, lenalidomide or pomalidomide routinely receive prophylaxis for thromboembolism. MM itself carries an increased risk of thromboembolism but this is significantly increased in those receiving thalidomide or its analogues. In a systematic review of thalidomide or lenalidomide use in MM the risk of thromboembolism was increased when either was used in combination with dexamethasone compared to when used use as monotherapy (3). It is not clear what the risk is in leprosy patients with ENL receiving thalidomide alone or in combination with corticosteroids.

5. Interestingly in a Canadian randomised controlled study of thalidomide and prednisone versus observation as maintenance therapy in MM there was not only a significant increase in thromboembolism in those treated with thalidomide and prednisone but also a significant reduction in health related quality of life (4).

6. There are different criteria used to define chronic ENL in studies. This is important as treatment strategies may differ in patients with acute, recurrent or chronic ENL. Published hospital studies suggest that chronic ENL is common.

What needs to be done?

1. Large, well designed prospective treatment studies clearly defined, relevant endpoints are needed to address how best to manage ENL This will require sufficient numbers of patients and will need to be multi-centre. It may need to take into account the treatments available in different countries.

2. In settings where thalidomide is available good data needs to be collected about the outcomes of organ involvement in ENL that is not sensitive to thalidomide.

3. There needs to be advocacy to promote the availability of thalidomide to treat ENL. The 8th Report of the WHO Expert Committee on Leprosy states "WHO...recommends its (thalidomide) use only under strict medical supervision in specialized referral facilities" (5). This recommendation is welcome however for many patients with ENL it is still not available or affordable.

4. Laboratory research to Improve the understanding of the pathophysiology of ENL needs to be undertaken

How can this be achieved?

I believe that this can be achieved through collaboration of those interested in ENL. The Erythema Nodosum Leprosum International STudy (ENLIST) Group was formed at a meeting in the Philippines in 2012 (2). It aims to improve: the understanding of the mechanisms which cause ENL, the evidence to guide treatment decisions and access to effective treatments.

The ENLIST Group presented work on the clinical features of ENL at the recent International Leprosy Congress and are actively seeking funding for further studies. We welcome expressions of interest from other centres interested in collaborating on ENL research.

Steve Walker

LSHTM

London, UK

References
1. Van Veen NH et al. Interventions for erythema nodosum leprosum.Cochrane Database Syst Rev. 2009 8;(3):CD006949 http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006949..pub2/pdf
2. Walker SL et al. International workshop on erythema nodosum leprosum (ENL) – consensus report; the formation of ENLIST, the ENL International STudy Group Lepr Rev (2012) 83, 396–407 www.lepra.org.uk/platforms/lepra/files/lr/Dec12/Lep396-407.pdf
3. Carrier M et al. Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost 2011; 9: 653–63. onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2011.04215.x/pdf
4. Stewart AK et al. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. http://bloodjournal.hematologylibrary.org/content/121/9/1517..long
5. WHO Expert Committee on Leprosy. 8th Report. www.searo.who.int/entity/global_leprosy.../8th_expert_comm_2012.pdf‎