Alimentary Pharmacology and Therapeutics Invited Editorials REFERENCES 1. Molina-Infante J, Hirano I. Editorial: expanding a narrow perspective on narrow caliber oesophagus in eosinophilic oesophagitis. Aliment Pharmacol Ther 2015; 41: 147–8.
Editorial: prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis P. Hendy & A. Hart IBD Unit, St Mark’s Hospital, Harrow, UK. E-mail: [email protected] doi:10.1111/apt.13011
In recent years, anti-tumour necrosis factor (TNF) drugs have been added to the medical armamentarium for patients with chronic active ulcerative colitis (UC). For those to whom these drugs are available, this has provided an important nonsurgical option. There are limited data about the success of adalimumab (ADA) to induce response after previous infliximab treatment. This study answers this important question and furthermore identifies factors which predict response.1 All patients in the study (n = 73) had previous exposure to IFX, early ADA levels available, and ≥1 year follow-up after commencing ADA therapy. Short-term response was defined as an improvement in the partial Mayo score at week 12, with long-term response defined as continued treatment with ADA, without the need for
Editorial: further evidence for the role of serum alkaline phosphatase as a useful surrogate marker of prognosis in PSC K. D. Williamson*,† & R. W. Chapman*,† *Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. † Nuffield Department of Experimental Medicine, Oxford University, Oxford, UK. E-mail: [email protected] doi:10.1111/apt.13004
The autoimmune liver disease, primary sclerosing cholangitis (PSC) remains an enigma; the aetiopathogenesis remains unknown, and medical treatment options are Aliment Pharmacol Ther 2015; 41: 145-152 ª 2014 John Wiley & Sons Ltd
2. Gentile N, Katzka D, Ravi K, et al. Oesophageal narrowing is common and frequently under-appreciated at endoscopy in patients with oesophageal eosinophilia. Aliment Pharmacol Ther 2015; 41: 99–107.
corticosteroids by week 52. Overall response rates were 75% and 52% at weeks 12 and 52, respectively. Nonresponders to IFX were less likely to respond to ADA than those who stopped IFX for other reasons. Response was also predicted by higher early ADA levels, with levels >4.5 lg/mL at 4 weeks predicting 12-week response, and levels >7 lg/mL at 4 weeks predicting 52-week response. The key message from this study is that nonresponse, loss of response or drug reaction to IFX does not denote a class effect necessitating abandonment of anti-TNF, and that ADA is a good second-line treatment in such patients. The prognostic value of performing anti-TNF drug and anti-drug antibody testing is also demonstrated, and this could hold the key to the improved patient selection which might alter the cost to benefit ratio for this class of therapies.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCE 1. Baert F, Vande Casteele N, Tops S, et al. Prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis. Aliment Pharmacol Ther 2014; 40: 1324–32.
limited.1 However, whilst earlier studies from tertiary centres suggested a median survival of 8–10 years, recent studies have shown a median survival of 21 years.2 With the advent of new therapies in development for PSC, the need for accurate surrogate endpoints in place of survival free of liver transplantation or death has become increasingly important. Prognostic models using clinical and biochemical data have not proved to be reliable.3 In a recent issue of AP&T the study from Rupp et al. has added weight to the increasing evidence base suggesting a valuable role of serum alkaline phosphatase (ALP) as a biomarker in predicting the clinical outcome of PSC.4 They prospectively evaluated 215 patients with PSC admitted to a single centre in Germany, and 149
Invited Editorials Table 1 | Comparison of Rupp et al.3 with previous studies evaluating alkaline phosphatase as a biomarker of clinical outcome in primary sclerosing cholangitis
Study
Site
n
Mean followup
Al Mamari et al.5
UK
139
10 years
ALP reduction to 40% drop of ALP from baseline
87
7 years
215
25 years
Lindstrom et al.6
Stanich et al.7
USA
Rupp et al.4
Germany
ALP outcome measure
Clinical endpoint
Proportion meeting ALP reduction
Primary outcome (ALP reduction vs. no reduction)
Liver decompensation, LT, liver-related death (including CC) Death, LT, CC
40%
6% vs. 38% reached clinical endpoint (P < 0.0001)
41%
ALP normalisation
Death, LT, CC
40%
ALP reduction to
Editorial: prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis P. Hendy & A. Hart IBD Unit, St Mark’s Hospital, Harrow, UK. E-mail: [email protected] doi:10.1111/apt.13011
In recent years, anti-tumour necrosis factor (TNF) drugs have been added to the medical armamentarium for patients with chronic active ulcerative colitis (UC). For those to whom these drugs are available, this has provided an important nonsurgical option. There are limited data about the success of adalimumab (ADA) to induce response after previous infliximab treatment. This study answers this important question and furthermore identifies factors which predict response.1 All patients in the study (n = 73) had previous exposure to IFX, early ADA levels available, and ≥1 year follow-up after commencing ADA therapy. Short-term response was defined as an improvement in the partial Mayo score at week 12, with long-term response defined as continued treatment with ADA, without the need for
Editorial: further evidence for the role of serum alkaline phosphatase as a useful surrogate marker of prognosis in PSC K. D. Williamson*,† & R. W. Chapman*,† *Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. † Nuffield Department of Experimental Medicine, Oxford University, Oxford, UK. E-mail: [email protected] doi:10.1111/apt.13004
The autoimmune liver disease, primary sclerosing cholangitis (PSC) remains an enigma; the aetiopathogenesis remains unknown, and medical treatment options are Aliment Pharmacol Ther 2015; 41: 145-152 ª 2014 John Wiley & Sons Ltd
2. Gentile N, Katzka D, Ravi K, et al. Oesophageal narrowing is common and frequently under-appreciated at endoscopy in patients with oesophageal eosinophilia. Aliment Pharmacol Ther 2015; 41: 99–107.
corticosteroids by week 52. Overall response rates were 75% and 52% at weeks 12 and 52, respectively. Nonresponders to IFX were less likely to respond to ADA than those who stopped IFX for other reasons. Response was also predicted by higher early ADA levels, with levels >4.5 lg/mL at 4 weeks predicting 12-week response, and levels >7 lg/mL at 4 weeks predicting 52-week response. The key message from this study is that nonresponse, loss of response or drug reaction to IFX does not denote a class effect necessitating abandonment of anti-TNF, and that ADA is a good second-line treatment in such patients. The prognostic value of performing anti-TNF drug and anti-drug antibody testing is also demonstrated, and this could hold the key to the improved patient selection which might alter the cost to benefit ratio for this class of therapies.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCE 1. Baert F, Vande Casteele N, Tops S, et al. Prior response to infliximab and early serum drug concentrations predict effects of adalimumab in ulcerative colitis. Aliment Pharmacol Ther 2014; 40: 1324–32.
limited.1 However, whilst earlier studies from tertiary centres suggested a median survival of 8–10 years, recent studies have shown a median survival of 21 years.2 With the advent of new therapies in development for PSC, the need for accurate surrogate endpoints in place of survival free of liver transplantation or death has become increasingly important. Prognostic models using clinical and biochemical data have not proved to be reliable.3 In a recent issue of AP&T the study from Rupp et al. has added weight to the increasing evidence base suggesting a valuable role of serum alkaline phosphatase (ALP) as a biomarker in predicting the clinical outcome of PSC.4 They prospectively evaluated 215 patients with PSC admitted to a single centre in Germany, and 149
Invited Editorials Table 1 | Comparison of Rupp et al.3 with previous studies evaluating alkaline phosphatase as a biomarker of clinical outcome in primary sclerosing cholangitis
Study
Site
n
Mean followup
Al Mamari et al.5
UK
139
10 years
ALP reduction to 40% drop of ALP from baseline
87
7 years
215
25 years
Lindstrom et al.6
Stanich et al.7
USA
Rupp et al.4
Germany
ALP outcome measure
Clinical endpoint
Proportion meeting ALP reduction
Primary outcome (ALP reduction vs. no reduction)
Liver decompensation, LT, liver-related death (including CC) Death, LT, CC
40%
6% vs. 38% reached clinical endpoint (P < 0.0001)
41%
ALP normalisation
Death, LT, CC
40%
ALP reduction to
