JEADV
LETTER TO THE EDITOR
Malignancy while on biologics in the treatment of psoriasis. A Case series Editor The advent of biologic therapy has radically improved the treatment of psoriasis. The efficacy and safety profiles of biologic therapies have been extensively evaluated over recent years with maturing data raising some potential long-term risks to malignancies.1 In particular lymphoma and skin cancers have been linked to the use of anti-TNF alpha agents.2–4 In this retrospective study, we analysed 115 psoriasis patients treated with biologic therapy over the past 10 years (2003– 2013). Six patients (four males: two females) with mean age 62.8 years developed a malignancy while receiving biologics. The mean time on biologic therapy to malignancy diagnosis was 38.6 months. In three patients, time interval between malignancy diagnosis and death ranged from 6 months to 6 years, while the remaining three patients are still alive, time interval from malignancy diagnosis to present ranges from 3 to 5 years. A brief history of all six patients is described in Table 1. Patient 1, a 47-year-old lady non-smoker, commenced on etanercept in 2006. After 10 months, she was diagnosed with ovarian carcinoma. In April 2007, she developed liver metastasis and subsequently died in 2010. Patient 2, a 79-year-old male was commenced on etanercept in 2004. He was diagnosed with small bowel adenocarcinoma in 2009 and etanercept was stopped. He later developed metastatic disease to the bladder and liver and died in 2012. Patient 3, a 70-year-old male with erythrodermic psoriasis in 2006 was commenced on etanercept in 2007 for recalcitrant psoriasis. In 2012, he was switched to adalimumab due to loss of efficacy. He was diagnosed with oesophageal carcinoma and later died in 2012. Patient 4, a 59-year-old male, smoker was commenced on etanercept in 2004 and later switched to efalizumab because of refractory psoriasis. In 2009, efalizumab was withdrawn from
JEADV 2015
the market, so he received adalimumab until his diagnosis of rectal adenocarcinoma in 2011. Post-cancer diagnosis, his psoriasis is partially controlled with acitretin therapy. Patient 5, a 64-year-old male non-smoker started on etanercept in 2008 and afterwards changed to adalimumab in 2009. Later that year he developed a malignant melanoma on his left ear. Patient 6, a 58-year-old lady non-smoker, was commenced on adalimumab in 2010. In late 2011, a ductal carcinoma of breast was diagnosed and adalimumab was stopped. She is currently managed with intermittent courses of NB-UVB. Managing severe psoriasis can be challenging in the face of a recent or current diagnosis of malignancy, as biologic therapy should be avoided for 5 years according to the BAD guidelines.5 Cessation of biologic therapy can result in severe relapse of psoriasis and in some patients the increasing severity of psoriasis may have a more negative impact for the patient than the actual malignancy diagnosis. In these circumstances, both the physician and the patient need to weigh the risks against the benefits of selecting alternative treatment methods. It has to be acknowledged that all six patients were exposed to systemic treatments before starting biologics and it may be the case that malignancies while taking biologics are more common because of the preceding immunosuppressive burden. In five of our six patients, systemic therapy was introduced following malignancy diagnosis but despite this approach, they had recalcitrant psoriasis with suboptimal control. Until more data including information on the cancer risk profile of biologic and systemic therapies are available, through the ongoing dermatology intervention registries, it is difficult to postulate if the solid tumours observed in our cohort are related or not, to biologic therapy. Our experience, also confirmed that there are limited treatment options for psoriasis patients who develop malignancy. A. Alani,* K. Ahmad, M. Sadlier, B. Ramsay Department of Dermatology, University Hospital Limerick, Limerick, Ireland *Correspondence: A. Alani. E-mail: [email protected]
© 2015 European Academy of Dermatology and Venereology
JEADV 2015
59/M
4
NB-UVB (2007)
Psoriatic arthritis
Cyclosporin (2009)
Psoriatic arthritis
HTN
Non-smoker
FAE/ (2009–2011)
FAE (2005–2007)
DM, obesity
Hyperlipidaemia
NB-UVB (2004)
Non-smoker
HTN
Alcohol liver disease
Obesity
MTX (2003–2004)
Smoker
Obesity, CVD
Alcoholic
Chronic Alcoholic
Cyclosporine/ (2006–2007)
MTX/ (2000–2004)
NB-UVB 5 courses (2000–2003)
Previous conventional psoriasis treatments/ duration
Smoker
Hyperlipidaemia
HTN
Smoker
HTN
Non-smoker
Co-morbidities
Small bowel adenocarcinoma (2009)
Etanercept (2004–2009)
Adalimumab/6 months (2011)
Etanercept (2008–2009)
Adalimumab (2009–2011)
Efalizumab (2005–2009)
Etanercept (2004)
Adalimumab (2012)
Breast carcinoma (2011)
SSMM (2009)
Rectal adenocarcinoma (2011)
Oesophageal carcinoma (2012)
Ovarian carcinoma (2004)
Etanercept (2004)
Etanercept (2007–2012)
Malignancy
Biologic therapy/duration
2 years
5 years
8 years
5.5 years
6 months
10 months
7 years
5 years
5 years
10 months
No conventional treatment
9 years
Duration from initiation of first biologic therapy to malignancy diagnosis
Duration from initiation of first conventional therapy to malignancy diagnosis
3 years still alive
5 years still alive
3 years still alive
6 months died in 2012
3 years died in 2012
6 years died in 2010
Duration from diagnosis of malignancy to outcome
Adalimumab (2013), NB-UVB (2014)
Acitretin (2012–2013)
Etanercept restarted (2010–2011), MTX (2011 – to date)
Current treatment: Acitretin commenced in 2012.
Topical tar and steroids
Acitretin (2009–2012)
NB-UVB (3 courses, 2007–2009), Etanercept (2009–2010)
Cyclosporin (2006)
FAE (2005–2006)
Treatment following malignancy diagnosis
HTN, hypertension; DM, Diabetes; CVD, cardiovascular disease; NB-UVB, narrow band ultraviolet light; MTX, methotrexate; FAE, fumaric acid ester; SSMM, superficial spreading malignant melanoma.
58/F
70/M
3
6
79/M
2
64/M
47/F
1
5
Age/sex
Patient
Table 1 Patient profile
2
Letter to the Editor
© 2015 European Academy of Dermatology and Venereology
Letter to the Editor
References 1 Patel RV, Clark LN, Lebwohl M et al. Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol 2009; 60: 1001–1017. 2 Gelfand JM, Shin DB, Neimann AL et al. The risk of lymphoma in patients with psoriasis. J Invest Dermatol 2006; 126: 2194–2201. 3 Nardone B, Hammel JA, Raisch DW et al. Melanoma associated with tumour necrosis alpha inhibitors: a Research on Adverse Drug Events and Reports (RADAR) project. Br J Dermatol 2014; 170: 1170–1172.
JEADV 2015
3
4 Girolomoni G, Altomare G, Ayala F et al. Safety of anti-TNF alpha agents in the treatment of psoriasis and psoriatic arthritis. Immunopharmacol Immunotoxicol 2012; 34: 548–560. 5 Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161: 987–1019. DOI: 10.1111/jdv.12982
© 2015 European Academy of Dermatology and Venereology
LETTER TO THE EDITOR
Malignancy while on biologics in the treatment of psoriasis. A Case series Editor The advent of biologic therapy has radically improved the treatment of psoriasis. The efficacy and safety profiles of biologic therapies have been extensively evaluated over recent years with maturing data raising some potential long-term risks to malignancies.1 In particular lymphoma and skin cancers have been linked to the use of anti-TNF alpha agents.2–4 In this retrospective study, we analysed 115 psoriasis patients treated with biologic therapy over the past 10 years (2003– 2013). Six patients (four males: two females) with mean age 62.8 years developed a malignancy while receiving biologics. The mean time on biologic therapy to malignancy diagnosis was 38.6 months. In three patients, time interval between malignancy diagnosis and death ranged from 6 months to 6 years, while the remaining three patients are still alive, time interval from malignancy diagnosis to present ranges from 3 to 5 years. A brief history of all six patients is described in Table 1. Patient 1, a 47-year-old lady non-smoker, commenced on etanercept in 2006. After 10 months, she was diagnosed with ovarian carcinoma. In April 2007, she developed liver metastasis and subsequently died in 2010. Patient 2, a 79-year-old male was commenced on etanercept in 2004. He was diagnosed with small bowel adenocarcinoma in 2009 and etanercept was stopped. He later developed metastatic disease to the bladder and liver and died in 2012. Patient 3, a 70-year-old male with erythrodermic psoriasis in 2006 was commenced on etanercept in 2007 for recalcitrant psoriasis. In 2012, he was switched to adalimumab due to loss of efficacy. He was diagnosed with oesophageal carcinoma and later died in 2012. Patient 4, a 59-year-old male, smoker was commenced on etanercept in 2004 and later switched to efalizumab because of refractory psoriasis. In 2009, efalizumab was withdrawn from
JEADV 2015
the market, so he received adalimumab until his diagnosis of rectal adenocarcinoma in 2011. Post-cancer diagnosis, his psoriasis is partially controlled with acitretin therapy. Patient 5, a 64-year-old male non-smoker started on etanercept in 2008 and afterwards changed to adalimumab in 2009. Later that year he developed a malignant melanoma on his left ear. Patient 6, a 58-year-old lady non-smoker, was commenced on adalimumab in 2010. In late 2011, a ductal carcinoma of breast was diagnosed and adalimumab was stopped. She is currently managed with intermittent courses of NB-UVB. Managing severe psoriasis can be challenging in the face of a recent or current diagnosis of malignancy, as biologic therapy should be avoided for 5 years according to the BAD guidelines.5 Cessation of biologic therapy can result in severe relapse of psoriasis and in some patients the increasing severity of psoriasis may have a more negative impact for the patient than the actual malignancy diagnosis. In these circumstances, both the physician and the patient need to weigh the risks against the benefits of selecting alternative treatment methods. It has to be acknowledged that all six patients were exposed to systemic treatments before starting biologics and it may be the case that malignancies while taking biologics are more common because of the preceding immunosuppressive burden. In five of our six patients, systemic therapy was introduced following malignancy diagnosis but despite this approach, they had recalcitrant psoriasis with suboptimal control. Until more data including information on the cancer risk profile of biologic and systemic therapies are available, through the ongoing dermatology intervention registries, it is difficult to postulate if the solid tumours observed in our cohort are related or not, to biologic therapy. Our experience, also confirmed that there are limited treatment options for psoriasis patients who develop malignancy. A. Alani,* K. Ahmad, M. Sadlier, B. Ramsay Department of Dermatology, University Hospital Limerick, Limerick, Ireland *Correspondence: A. Alani. E-mail: [email protected]
© 2015 European Academy of Dermatology and Venereology
JEADV 2015
59/M
4
NB-UVB (2007)
Psoriatic arthritis
Cyclosporin (2009)
Psoriatic arthritis
HTN
Non-smoker
FAE/ (2009–2011)
FAE (2005–2007)
DM, obesity
Hyperlipidaemia
NB-UVB (2004)
Non-smoker
HTN
Alcohol liver disease
Obesity
MTX (2003–2004)
Smoker
Obesity, CVD
Alcoholic
Chronic Alcoholic
Cyclosporine/ (2006–2007)
MTX/ (2000–2004)
NB-UVB 5 courses (2000–2003)
Previous conventional psoriasis treatments/ duration
Smoker
Hyperlipidaemia
HTN
Smoker
HTN
Non-smoker
Co-morbidities
Small bowel adenocarcinoma (2009)
Etanercept (2004–2009)
Adalimumab/6 months (2011)
Etanercept (2008–2009)
Adalimumab (2009–2011)
Efalizumab (2005–2009)
Etanercept (2004)
Adalimumab (2012)
Breast carcinoma (2011)
SSMM (2009)
Rectal adenocarcinoma (2011)
Oesophageal carcinoma (2012)
Ovarian carcinoma (2004)
Etanercept (2004)
Etanercept (2007–2012)
Malignancy
Biologic therapy/duration
2 years
5 years
8 years
5.5 years
6 months
10 months
7 years
5 years
5 years
10 months
No conventional treatment
9 years
Duration from initiation of first biologic therapy to malignancy diagnosis
Duration from initiation of first conventional therapy to malignancy diagnosis
3 years still alive
5 years still alive
3 years still alive
6 months died in 2012
3 years died in 2012
6 years died in 2010
Duration from diagnosis of malignancy to outcome
Adalimumab (2013), NB-UVB (2014)
Acitretin (2012–2013)
Etanercept restarted (2010–2011), MTX (2011 – to date)
Current treatment: Acitretin commenced in 2012.
Topical tar and steroids
Acitretin (2009–2012)
NB-UVB (3 courses, 2007–2009), Etanercept (2009–2010)
Cyclosporin (2006)
FAE (2005–2006)
Treatment following malignancy diagnosis
HTN, hypertension; DM, Diabetes; CVD, cardiovascular disease; NB-UVB, narrow band ultraviolet light; MTX, methotrexate; FAE, fumaric acid ester; SSMM, superficial spreading malignant melanoma.
58/F
70/M
3
6
79/M
2
64/M
47/F
1
5
Age/sex
Patient
Table 1 Patient profile
2
Letter to the Editor
© 2015 European Academy of Dermatology and Venereology
Letter to the Editor
References 1 Patel RV, Clark LN, Lebwohl M et al. Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol 2009; 60: 1001–1017. 2 Gelfand JM, Shin DB, Neimann AL et al. The risk of lymphoma in patients with psoriasis. J Invest Dermatol 2006; 126: 2194–2201. 3 Nardone B, Hammel JA, Raisch DW et al. Melanoma associated with tumour necrosis alpha inhibitors: a Research on Adverse Drug Events and Reports (RADAR) project. Br J Dermatol 2014; 170: 1170–1172.
JEADV 2015
3
4 Girolomoni G, Altomare G, Ayala F et al. Safety of anti-TNF alpha agents in the treatment of psoriasis and psoriatic arthritis. Immunopharmacol Immunotoxicol 2012; 34: 548–560. 5 Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161: 987–1019. DOI: 10.1111/jdv.12982
© 2015 European Academy of Dermatology and Venereology
