Letters to the Editors
Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet – authors’ reply K. Kaukinen* & P. S. Daugherty† *Department of Gastroenterology and Alimentary Tract Surgery, Univeristy of Tampere, Tampere, Finland. † Department of Chemical Engineering, University of California, Santa Barbara, CA, USA. E-mail: [email protected] doi:10.1111/apt.12729
SIRS, We thank Professor Matuchansky for his comments concerning our manuscript.1, 2 Continued gluten ingestion is surely the leading cause of nonresponsive coeliac disease. Similar to our patient series, some patients suffering from type 1 or 2 refractory coeliac disease have been reported to have low positive serum transglutaminase 2-antibody levels, despite a strict gluten-free diet.2–5 This might be considered as a sign of ongoing gluten ingestion and one could argue that these patients have been mis-classified as having truly nonresponsive condition. Due to the lack of reliable tools it is often challenging to uncover minor dietary lapses or inadvertent gluten intake. In Finland, there is a high prevalence of clinically diagnosed coeliac disease, and the majority (approximately 90%) of the patients adhere to a strict gluten-free diet. On a long-term gluten-free diet intestinal mucosa recovers in 96% of coeliac patients, and the prevalence of refractory coeliac disease is rare in Finland.6 In the current study,2 nonresponsive coeliac disease patients were from this well-defined patient cohort. The patients here had been followed up for a median of 10 years (up to 30 years) meaning that dietary adherence had been rigorously assessed not only once but several times over the years. In addition to 4-day food records, the
Letter: biological drugs for inducing remission in ulcerative colitis D. Maratea*, V. Fadda*, S. Trippoli*, R. Gatto*, M. De Rosa†, C. Marinai‡ & A. Messori* *HTA Unit, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. † SIFACT, Italian Society for Clinical Pharmacy and Therapeutics, Milan, Italy. ‡ Department of Pharmaceutical Logistics, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. E-mail: [email protected] doi:10.1111/apt.12690 1242
patients had been interviewed repeatedly by a trained dietitian and coeliac disease experts to uncover hidden gluten traces. Based on these assessments, the strictness of the gluten-free diets of nonresponsive cases was equivalent to that of responsive cases. Finally, regardless of the impact of trace gluten ingestion, the anti-deamidated gliadin peptide assays described were able to distinguish histologically nonresponsive patients from histologically responsive patients with high accuracy. With regard to the second point, we have applied the definition of latent refractory coeliac disease as previously introduced,5 wherein symptoms are required for a diagnosis of refractory coeliac disease, and did not manifest in the latent group until sometime after blood was collected.
ACKNOWLEDGEMENTS The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Matuchansky C. Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet. Aliment Pharmacol Ther 2014; 39: 1241. 2. Spatola BN, Kaukinen K, Collin P, Mäki M, Kagnoff MF, Daugherty PS. Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease. Aliment Pharmacol Ther 2014; 39: 407–17. 3. Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA. Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology 2009; 136: 99–107. 4. Roshan B, Leffler DA, Jamma S, et al. The incidence and clinical spectrum of refractory celiac disease in a north american referral center. Am J Gastroenterol 2011; 106: 923–8. 5. Kaukinen K, Peräaho M, Lindfors K, et al. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther 2007; 25: 1237–45. 6. Ilus T, Kaukinen K, Virta LJ, et al. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment Pharmacol Ther 2014; 39: 418–25.
SIRS, When nonsignificant results are found in trials or meta-analyses, differentiating between no proof of difference (an ‘inconclusive’ result)1 and proof of no difference (equivalence, a ‘conclusive’ result)1 is increasingly recognised to be a crucial step for a correct interpretation.2–4 We have reanalysed the trials examined by Stidham and co-workers5 for the end-point of induction of remission. Firstly, the meta-analysis results were re-expressed using risk difference (RD) rather than relative risk.6 Then, the pooled RDs for direct comparisons of biologics vs placebo were subjected to network meta-analysis. In this way, the pooled values of RD were estimated for the Aliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
Letters to the Editors three indirect head-to-head comparisons between individual biologics. The results of our network meta-analysis revealed nonsignificant differences in all indirect comparisons (Figure 1a). Then, we extended our analysis by performing an equivalence test1–4 among these three biologics. Testing equivalence requires that a margin is pre-specified to separate clinically relevant improvements in the outcome from
(a)
Adalimumab = =
RD = 0.07 (95% CI: –0.067 to 0.207)
= t
RD = 0.077 (95% CI: 0.031 to 0.124)
+ RD = –0.047 (95% CI: –0.12 to 0.026)
= t
= t
Infliximab
= RD = 0.023 (95% CI: –0.118 to 0.164)
+
Golimumab +
ACKNOWLEDGEMENT Declaration of personal and funding interests: None.
RD = 0.124 (95% CI: 0.068 to 0.180)
RD = 0.147 (95% CI: 0.018 to 0.276)
clinically irrelevant ones.1 Margins can be retrieved from the statistical power sections of original trials. According to this procedure, we adopted the margin of 12% employed by Reinisch et al.7 and we finally combined, in a Forest plot, this margin with the RD values for indirect comparisons. Equivalence testing frequently relies on these Forest plots.1–4 Based on our equivalence testing, the comparisons of infliximab vs. adalimumab or golimumab (Figure 1b) showed no proof of difference, but failed to demonstrate proof of no difference (i.e. equivalence). So, these two comparisons remained inconclusive. More interestingly, the indirect comparison between the two subcutaneous agents (adalimumab vs. golimumab) showed proof of no difference (i.e. a conclusive result). In conclusion, this latter finding indicates equivalence of these two subcutaneous agents at least for this therapeutic indication. One limitation of this analytical approach is that margins intrinsically have a certain degree of arbitrariness.8
– –
REFERENCES
–
Placebo (b)
–25
–20
–15
–10 –5 0 5 10 Difference (%) in remission rate
15
20
25
1. Ahn S, Park SH, Lee KH. How to demonstrate similarity by using noninferiority and equivalence statistical testing in radiology research. Radiology 2013; 267: 328–38. 2. Messori A, Fadda V, Maratea D, Trippoli S. Outcomes with shortterm versus long-term antiplatelet dual therapy after drug-eluting stenting: quantifying the equivalence margins. Int J Cardiol 2014; 172: 469–70. 3. Messori A, Maratea D, Fadda V, Trippoli S. Risk of intracranial haemorrhage in patients with atrial fibrillation treated with novel oral anticoagulants: testing the equivalence margins between dabigratran, rivaroxaban and apixaban. Eur J Clin Pharmacol 2014; 70: 505–6. 4. Messori A, Fadda V, Maratea D, Trippoli S. Rates of inhibitor development in previously untreated patients with severe
Figure 1 | Head-to-head indirect comparisons of three biological treatments for inducing remission in ulcerative colitis: network meta-analysis (a) and equivalence testing based on a Forest plot (b). The outcome measure for each of these indirect pair-wise comparisons was the achievement of remission (expressed as a percentage). The meta-analytic values of RD (with 95%CIs) were extracted from reference 2. (a) This type of graph (simplified figure according to Fadda et al.9) summarises the results, but does not allow us to differentiate between “no proof of difference” and “proof of no difference”. Statistical calculations according to Bucher et al.10 +, more effective at statistical level of P < 0.05; , less effective at statistical level of P < 0.05; =, no difference; t, indicates which treatment is favoured by a trend in cases of no difference. RD, risk difference; CI, confidence interval. (b) The equivalence test is based on the area comprised between the two vertical dashed lines that reflect the pre-determined equivalence margins (from 12% to +12%). Each horizontal bar indicates the two-sided 95%CI for the RD (solid square). The criterion for demonstrating equivalence is when both extremes of the 95%CI remain within the two vertical dashed lines. Comparisons: [1] infliximab vs. adalimumab (in green): RD = 7% (95% CI: 6.7% to 20.7%); [2] infliximab vs. golimumab (in brown): RD = 2.3% (95% CI: 11.8% to 16.4%); [3] adalimumab vs. golimumab (in blue): RD = 4.7% (95% CI: 12% to 2.6%). Aliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
1243
Letters to the Editors haemophilia A treated with plasma-derived or recombinant Factor VIII: no proof of difference or proof of no difference? Semin Thromb Hemost 2014; 40: 269–70. 5. Stidham RW, Lee TC, Higgins PD, et al. Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 660–71. 6. Messori A, Fadda V, Gatto R, Maratea D, Trippoli S. PubMed Commons (comment). Available at: http://www.ncbi.nlm.nih. gov/pubmed/24506179. Accessed February 12, 2014. 7. Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely
Letter: biological drugs for inducing remission in ulcerative colitis – authors’ reply R. W. Stidham*, T. C. H. Lee†, P. D. R. Higgins*, A. R. Deshpande‡, D. A. Sussman‡, A. G. Singal§, B. J. Elmunzer*, S. D. Saini*,¶, S. Vijan†,¶ & A. K. Waljee*,¶ *Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA. † University of Michigan, Ann Arbor, MI, USA. ‡ University of Miami Miller School of Medicine, Miami, FL, USA. § UT Southwestern Medical Center, Dallas, TX, USA. ¶ Ann Arbor Veterans Affairs Healthcare System, Ann Arbor, MI, USA. E-mail: [email protected] doi:10.1111/apt.12724
SIRS, We thank Maratea et al. for their insightful comments.1 Network meta-analyses (NMAs) are becoming increasingly common in the medical literature. Various analytic techniques are available for NMAs. In our study,2 we used a Bayesian-driven approach with uninformed priors and found only nonsignificant trends when comparing anti-tumour necrosis factor (TNF) agents for both remission and response. We agree that it is important to differentiate between “no proof of difference” (i.e., an inconclusive result) and
Letter: TNFa blockers and psoriasis: a ‘reasonable paradox’ – the role of TH-17 cells A. Sartini*, M. Di Girolamo*, A. Scarcelli*, A. Bertani*, L. Marzi*, C. Lasagni†, A. Merighi* & E. Villa* *Gastroenterology Unit, Policlinico di Modena, Modena, Italy. † Dermatology Unit, Policlinico di Modena, Modena, Italy. 1244
active ulcerative colitis: results of a randomised controlled trial. Gut 2011; 60: 780–7. 8. Norman G, Monteiro S, Salama S. Sample size calculations: should the emperor’s clothes be off the peg or made to measure? BMJ 2012; 23: e5278. 9. Fadda V, Maratea D, Trippoli S, Messori A. Network metaanalysis. Results can be summarised in a simple figure. BMJ 2011; 23: d1555. 10. Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997; 50: 683–91.
“proof of no difference” (i.e., equivalence) and find the results by Maratea and colleagues interesting. However, as the authors point out, their conclusions are based on an underlying assumption (margin of 12%), which has a “certain degree of arbitrariness”. Thus, despite its sophistication, even this approach is also inherently inconclusive regarding definite superiority or equivalence among anti-TNF agents. Until more conclusive data are available, we believe that other factors such as preference, safety, cost and route of administration should dictate choice of anti-TNF agents. Ultimately, a randomised controlled trial among anti-TNF agents in UC is of practical size and should be performed.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Maratea D, Fadda V, Trippoli S, et al. Letter: biological drugs for inducing remission in ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 1242–4. 2. Stidham RW, Lee TCH, Higgins PDR, et al. Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 660–71.
E-mail: [email protected] doi:10.1111/apt.12705
SIRS, We read with interest the review by Moran and colleagues on dermatological complications of immunosuppressive therapies for inflammatory bowel disease (IBD), particularly anti-tumour necrosis factor alpha (TNFa)-inAliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet – authors’ reply K. Kaukinen* & P. S. Daugherty† *Department of Gastroenterology and Alimentary Tract Surgery, Univeristy of Tampere, Tampere, Finland. † Department of Chemical Engineering, University of California, Santa Barbara, CA, USA. E-mail: [email protected] doi:10.1111/apt.12729
SIRS, We thank Professor Matuchansky for his comments concerning our manuscript.1, 2 Continued gluten ingestion is surely the leading cause of nonresponsive coeliac disease. Similar to our patient series, some patients suffering from type 1 or 2 refractory coeliac disease have been reported to have low positive serum transglutaminase 2-antibody levels, despite a strict gluten-free diet.2–5 This might be considered as a sign of ongoing gluten ingestion and one could argue that these patients have been mis-classified as having truly nonresponsive condition. Due to the lack of reliable tools it is often challenging to uncover minor dietary lapses or inadvertent gluten intake. In Finland, there is a high prevalence of clinically diagnosed coeliac disease, and the majority (approximately 90%) of the patients adhere to a strict gluten-free diet. On a long-term gluten-free diet intestinal mucosa recovers in 96% of coeliac patients, and the prevalence of refractory coeliac disease is rare in Finland.6 In the current study,2 nonresponsive coeliac disease patients were from this well-defined patient cohort. The patients here had been followed up for a median of 10 years (up to 30 years) meaning that dietary adherence had been rigorously assessed not only once but several times over the years. In addition to 4-day food records, the
Letter: biological drugs for inducing remission in ulcerative colitis D. Maratea*, V. Fadda*, S. Trippoli*, R. Gatto*, M. De Rosa†, C. Marinai‡ & A. Messori* *HTA Unit, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. † SIFACT, Italian Society for Clinical Pharmacy and Therapeutics, Milan, Italy. ‡ Department of Pharmaceutical Logistics, ESTAV Toscana Centro, Regional Health Service, Florence, Italy. E-mail: [email protected] doi:10.1111/apt.12690 1242
patients had been interviewed repeatedly by a trained dietitian and coeliac disease experts to uncover hidden gluten traces. Based on these assessments, the strictness of the gluten-free diets of nonresponsive cases was equivalent to that of responsive cases. Finally, regardless of the impact of trace gluten ingestion, the anti-deamidated gliadin peptide assays described were able to distinguish histologically nonresponsive patients from histologically responsive patients with high accuracy. With regard to the second point, we have applied the definition of latent refractory coeliac disease as previously introduced,5 wherein symptoms are required for a diagnosis of refractory coeliac disease, and did not manifest in the latent group until sometime after blood was collected.
ACKNOWLEDGEMENTS The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Matuchansky C. Letter: nonresponsive coeliac disease and evaluation of the strictness of a gluten-free diet. Aliment Pharmacol Ther 2014; 39: 1241. 2. Spatola BN, Kaukinen K, Collin P, Mäki M, Kagnoff MF, Daugherty PS. Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease. Aliment Pharmacol Ther 2014; 39: 407–17. 3. Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA. Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology 2009; 136: 99–107. 4. Roshan B, Leffler DA, Jamma S, et al. The incidence and clinical spectrum of refractory celiac disease in a north american referral center. Am J Gastroenterol 2011; 106: 923–8. 5. Kaukinen K, Peräaho M, Lindfors K, et al. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther 2007; 25: 1237–45. 6. Ilus T, Kaukinen K, Virta LJ, et al. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment Pharmacol Ther 2014; 39: 418–25.
SIRS, When nonsignificant results are found in trials or meta-analyses, differentiating between no proof of difference (an ‘inconclusive’ result)1 and proof of no difference (equivalence, a ‘conclusive’ result)1 is increasingly recognised to be a crucial step for a correct interpretation.2–4 We have reanalysed the trials examined by Stidham and co-workers5 for the end-point of induction of remission. Firstly, the meta-analysis results were re-expressed using risk difference (RD) rather than relative risk.6 Then, the pooled RDs for direct comparisons of biologics vs placebo were subjected to network meta-analysis. In this way, the pooled values of RD were estimated for the Aliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
Letters to the Editors three indirect head-to-head comparisons between individual biologics. The results of our network meta-analysis revealed nonsignificant differences in all indirect comparisons (Figure 1a). Then, we extended our analysis by performing an equivalence test1–4 among these three biologics. Testing equivalence requires that a margin is pre-specified to separate clinically relevant improvements in the outcome from
(a)
Adalimumab = =
RD = 0.07 (95% CI: –0.067 to 0.207)
= t
RD = 0.077 (95% CI: 0.031 to 0.124)
+ RD = –0.047 (95% CI: –0.12 to 0.026)
= t
= t
Infliximab
= RD = 0.023 (95% CI: –0.118 to 0.164)
+
Golimumab +
ACKNOWLEDGEMENT Declaration of personal and funding interests: None.
RD = 0.124 (95% CI: 0.068 to 0.180)
RD = 0.147 (95% CI: 0.018 to 0.276)
clinically irrelevant ones.1 Margins can be retrieved from the statistical power sections of original trials. According to this procedure, we adopted the margin of 12% employed by Reinisch et al.7 and we finally combined, in a Forest plot, this margin with the RD values for indirect comparisons. Equivalence testing frequently relies on these Forest plots.1–4 Based on our equivalence testing, the comparisons of infliximab vs. adalimumab or golimumab (Figure 1b) showed no proof of difference, but failed to demonstrate proof of no difference (i.e. equivalence). So, these two comparisons remained inconclusive. More interestingly, the indirect comparison between the two subcutaneous agents (adalimumab vs. golimumab) showed proof of no difference (i.e. a conclusive result). In conclusion, this latter finding indicates equivalence of these two subcutaneous agents at least for this therapeutic indication. One limitation of this analytical approach is that margins intrinsically have a certain degree of arbitrariness.8
– –
REFERENCES
–
Placebo (b)
–25
–20
–15
–10 –5 0 5 10 Difference (%) in remission rate
15
20
25
1. Ahn S, Park SH, Lee KH. How to demonstrate similarity by using noninferiority and equivalence statistical testing in radiology research. Radiology 2013; 267: 328–38. 2. Messori A, Fadda V, Maratea D, Trippoli S. Outcomes with shortterm versus long-term antiplatelet dual therapy after drug-eluting stenting: quantifying the equivalence margins. Int J Cardiol 2014; 172: 469–70. 3. Messori A, Maratea D, Fadda V, Trippoli S. Risk of intracranial haemorrhage in patients with atrial fibrillation treated with novel oral anticoagulants: testing the equivalence margins between dabigratran, rivaroxaban and apixaban. Eur J Clin Pharmacol 2014; 70: 505–6. 4. Messori A, Fadda V, Maratea D, Trippoli S. Rates of inhibitor development in previously untreated patients with severe
Figure 1 | Head-to-head indirect comparisons of three biological treatments for inducing remission in ulcerative colitis: network meta-analysis (a) and equivalence testing based on a Forest plot (b). The outcome measure for each of these indirect pair-wise comparisons was the achievement of remission (expressed as a percentage). The meta-analytic values of RD (with 95%CIs) were extracted from reference 2. (a) This type of graph (simplified figure according to Fadda et al.9) summarises the results, but does not allow us to differentiate between “no proof of difference” and “proof of no difference”. Statistical calculations according to Bucher et al.10 +, more effective at statistical level of P < 0.05; , less effective at statistical level of P < 0.05; =, no difference; t, indicates which treatment is favoured by a trend in cases of no difference. RD, risk difference; CI, confidence interval. (b) The equivalence test is based on the area comprised between the two vertical dashed lines that reflect the pre-determined equivalence margins (from 12% to +12%). Each horizontal bar indicates the two-sided 95%CI for the RD (solid square). The criterion for demonstrating equivalence is when both extremes of the 95%CI remain within the two vertical dashed lines. Comparisons: [1] infliximab vs. adalimumab (in green): RD = 7% (95% CI: 6.7% to 20.7%); [2] infliximab vs. golimumab (in brown): RD = 2.3% (95% CI: 11.8% to 16.4%); [3] adalimumab vs. golimumab (in blue): RD = 4.7% (95% CI: 12% to 2.6%). Aliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
1243
Letters to the Editors haemophilia A treated with plasma-derived or recombinant Factor VIII: no proof of difference or proof of no difference? Semin Thromb Hemost 2014; 40: 269–70. 5. Stidham RW, Lee TC, Higgins PD, et al. Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 660–71. 6. Messori A, Fadda V, Gatto R, Maratea D, Trippoli S. PubMed Commons (comment). Available at: http://www.ncbi.nlm.nih. gov/pubmed/24506179. Accessed February 12, 2014. 7. Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely
Letter: biological drugs for inducing remission in ulcerative colitis – authors’ reply R. W. Stidham*, T. C. H. Lee†, P. D. R. Higgins*, A. R. Deshpande‡, D. A. Sussman‡, A. G. Singal§, B. J. Elmunzer*, S. D. Saini*,¶, S. Vijan†,¶ & A. K. Waljee*,¶ *Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA. † University of Michigan, Ann Arbor, MI, USA. ‡ University of Miami Miller School of Medicine, Miami, FL, USA. § UT Southwestern Medical Center, Dallas, TX, USA. ¶ Ann Arbor Veterans Affairs Healthcare System, Ann Arbor, MI, USA. E-mail: [email protected] doi:10.1111/apt.12724
SIRS, We thank Maratea et al. for their insightful comments.1 Network meta-analyses (NMAs) are becoming increasingly common in the medical literature. Various analytic techniques are available for NMAs. In our study,2 we used a Bayesian-driven approach with uninformed priors and found only nonsignificant trends when comparing anti-tumour necrosis factor (TNF) agents for both remission and response. We agree that it is important to differentiate between “no proof of difference” (i.e., an inconclusive result) and
Letter: TNFa blockers and psoriasis: a ‘reasonable paradox’ – the role of TH-17 cells A. Sartini*, M. Di Girolamo*, A. Scarcelli*, A. Bertani*, L. Marzi*, C. Lasagni†, A. Merighi* & E. Villa* *Gastroenterology Unit, Policlinico di Modena, Modena, Italy. † Dermatology Unit, Policlinico di Modena, Modena, Italy. 1244
active ulcerative colitis: results of a randomised controlled trial. Gut 2011; 60: 780–7. 8. Norman G, Monteiro S, Salama S. Sample size calculations: should the emperor’s clothes be off the peg or made to measure? BMJ 2012; 23: e5278. 9. Fadda V, Maratea D, Trippoli S, Messori A. Network metaanalysis. Results can be summarised in a simple figure. BMJ 2011; 23: d1555. 10. Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997; 50: 683–91.
“proof of no difference” (i.e., equivalence) and find the results by Maratea and colleagues interesting. However, as the authors point out, their conclusions are based on an underlying assumption (margin of 12%), which has a “certain degree of arbitrariness”. Thus, despite its sophistication, even this approach is also inherently inconclusive regarding definite superiority or equivalence among anti-TNF agents. Until more conclusive data are available, we believe that other factors such as preference, safety, cost and route of administration should dictate choice of anti-TNF agents. Ultimately, a randomised controlled trial among anti-TNF agents in UC is of practical size and should be performed.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Maratea D, Fadda V, Trippoli S, et al. Letter: biological drugs for inducing remission in ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 1242–4. 2. Stidham RW, Lee TCH, Higgins PDR, et al. Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis. Aliment Pharmacol Ther 2014; 39: 660–71.
E-mail: [email protected] doi:10.1111/apt.12705
SIRS, We read with interest the review by Moran and colleagues on dermatological complications of immunosuppressive therapies for inflammatory bowel disease (IBD), particularly anti-tumour necrosis factor alpha (TNFa)-inAliment Pharmacol Ther 2014; 39: 1241-1252 ª 2014 John Wiley & Sons Ltd
