- Email: [email protected]
Effectiveness of sequential use of biologics in the treatment of moderate to severe psoriasis in real world Canadian academic clinical practice: A cohort study
J AM ACAD DERMATOL
176 Letters
JANUARY 2016
2. Coloe J, Morrell DS. Could higher doses of isotretinoin reduce the frequency of treatment failure in acne patients? J Am Acad Dermatol. 2011;65(2):422-423. 3. Blasiak RC, Stamey CR, Burkhart CN, et al. High-dose isotretinoin treatment and rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149(12): 1392-1398. 4. Absorica (isotretinoin) [ prescribing information]. Jacksonville, FL: Ranbaxy Laboratories Inc; 2014. 5. Gerhardstein PC, Hsu S, Liu A, et al. Relapse of acne following isotretinoin treatment: a retrospective study of 405 patients. J Drugs Dermatol. 2008;7(10):963. http://dx.doi.org/10.1016/j.jaad.2015.08.012
Effectiveness of sequential use of biologics in the treatment of moderate to severe psoriasis in real world Canadian academic clinical practice: A cohort study To the Editor: Biological agents are effective therapies for moderate to severe psoriasis.1 However, considerable variation in treatment response is observed in clinical practice,2 reflecting clinical and genetic heterogeneity of the disease as well as individual differences in drug metabolism and response, and suggesting that failure of 1 biologic does not preclude response to another biologic. In this large, multicenter study, we examine the effectiveness of adalimumab, etanercept, infliximab, and ustekinumab, and predictors of response to these treatments in patients with moderate to severe psoriasis following previous exposure to at least 1 biologic. Adult patients with psoriasis who failed treatment with at least 1 of the 4 biologics, defined as lack or loss of PASI 75 response/ physician global assessment (PGA) of 0 or 1 (clear and minimal disease, respectively) after $12 weeks of treatment, and then received another 1 of the 4 agents were included. Patients were treated at academic hospitals in Toronto, Ontario, Canada, between 2005 and 2014, and were followed up by the same dermatologist at every visit. Ethics approval was obtained. The number of psoriasis patients who achieved a significant response, defined as PASI 75 or PGA of 0 or 1 with at least 12 weeks of biologic therapy after previous biologic exposure, was quantified. Logistic regression was performed to determine potential predictors of treatment response using SAS version 9.3. Statistical significance was set as a 2-tailed P # .05. A total of 155 patients were included (Table I). A majority of patients who previously failed anti-tumor necrosis factor (TNF) therapy had a significant response to another anti-TNF or ustekinumab. Three of the 8 patients who failed ustekinumab therapy had a significant response to etanercept (Table II).
Table I. Clinical and demographic details: Baseline clinical and demographic data on 155 patients who were prescribed a tumor necrosis factor antagonist or ustekinumab and then switched to another biologic after treatment failure Variable
Median age in yr (IQR) Gender (N, %) Male Female Median disease duration in yrs (IQR) Comorbidities (N, % total) Psoriatic arthritis Inflammatory bowel disease Hypertension Dyslipidemia Diabetes Stroke Myocardial infarction Failed systemic therapies (N, % total) Methotrexate Acitretin Cyclosporine Phototherapy Baseline biologic (N, % total) Etanercept Adalimumab Infliximab Ustekinumab
Value
48.5 (19) 72/155 (46%) 83/155 (54%) 17.2 (15.0) 81/155 5/155 35/155 25/155 21/155 1/155 3/155
(52%) (3%) (22%) (16%) (13%) (1%) (2%)
98/155 50/155 34/155 109/155
(63%) (32%) (22%) (70%)
93/155 31/155 23/155 8/155
(60%) (20%) (15%) (5%)
IQR, Interquartile range; N, number of subjects meeting criteria.
Patients with 2 previously failed biologics were half as likely to respond to the present treatment compared to subjects with just 1 failed biologic (odds ratio: 0.474, 95% CI: 0.23-0.96, P ¼ .04). In patients who previously failed only 1 biologic, 45/75 (60%) of those who tried a different TNF antagonist and 36 of 43 (84%) of those who received ustekinumab achieved a significant response after 12 weeks of subsequent biologic therapy. In patients who previously failed 2 biologics, 4 of 8 (50%) of those who received another anti-TNF, and 11 of 22 (50%) of those who were given ustekinumab achieved clinically significant improvement. Of the 7 patients who previously failed 3 biologics, 4 of 7 (43%) achieved a significant improvement on another anti-TNF. Our results corroborate previously published findings of 65% efficacy, as defined by PASI 75 response, for etanercept,3 61% to 68% efficacy for adalimumab,4 and 66% for ustekinumab5 after these patients had failed at least 1 previous biologic. A recent study showed that in 105 patients who switched from a first to a second anti-TNF, a PASI 75 response was reached by 29% after 16 weeks and by 45.6% after 24 weeks.6 Differences in study design
J AM ACAD DERMATOL
Letters 177
VOLUME 74, NUMBER 1
Table II. Response rates of biologics among psoriasis patients with previous biologic exposure: Number and percentage of biologic-experienced patients who achieved significant improvement as defined by PASI 75 or PGA of 0 or 1 (clear and minimal disease, respectively) after 12 weeks of etanercept, infliximab, adalimumab, or ustekinumab New biologic (N = 155) Baseline biologic (n = 155) Etanercept (n = 23) Infliximab (n = 17) Adalimumab (n = 50) Ustekinumab (n = 65) Any anti-TNF (n = 90)
Etanercept (n = 93) Infliximab (n = 23) Adalimumab (n = 31) Ustekinumab (n = 8) Any anti-TNF (n = 147)
N/A 3/4 (75%) 7/11 (64%) 3/8 (38%) N/A
7/12 (58%) N/A 3/5 (60%) N/A N/A
24/43 (56%) 4/7 (57%) N/A N/A N/A
27/38 (71%) 9/12 (75%) 11/15 (73%) N/A 47/65 (72%)
31/55 7/11 10/16 3/8 48/82
(56%) (64%) (63%) (38%) (59%)
NA, Not applicable; TNF, tumor necrosis factor.
and patient populations should be considered when making comparisons. A significant improvement was defined as either PASI 75 response or PGA of 0 or 1 in this study, whereas the previous study only used PASI 75. A major limitation is the retrospective nature of this study. Another limitation may be that treatments were not completely standardized, randomized, or blinded. However, the data presented here came from ‘‘real world’’ clinical practice, thus rendering this study a valuable addition to the relatively limited literature on this topic. In summary, our results suggest that after failure of 1 anti-TNF, most patients are still likely to respond well to another biologic. Judy K. Qiang, BA,a Ali Shahbaz, BSc,b Whan Kim, BSc,c Joseph Marinas, BSc,c Simon Greaves, MSc,d and Jensen Yeung, MDe Faculty of Medicine,a University of Toronto; School of Medicine,b University of Ottawa, Ottawa; Michael G. DeGroote School of Medicine,c McMaster University, Hamilton; Dalla Lana School of Public Health,d University of Toronto, and Divison of Dermatology,e Department of Medicine, University of Toronto, Ontario, Canada. Funding source: None. Conflicts of interest: Dr Yeung serves as a speaker, consultant and investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, Janssen, Leo, Medimmune, Novartis, Pfizer, and Takeda. The other authors have no conflicts of interest to declare. Correspondence to: Dr Jensen Yeung, MD, Division of Dermatology, University of Toronto, 76 Grenville Street, 5th Floor, Toronto, ON, M5S 1B2, Canada E-mail: [email protected]
REFERENCES 1. Reich K, Nestle FO, Ortonne JP, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicenter, double-blind trial. Lancet. 2005; 366(9494):1367-1374. 2. Leman J, Burden AD. Sequential use of biologics in the treatment of moderate-to-severe plaque psoriasis. Br J Dermatol. 2012;167(Suppl 3):12-20. 3. Mazzotta A, Esposito M, Costanzo A, et al. Efficacy and safety of etanercept in psoriasis after switching from other treatments: an observational study. Am J Clin Dermatol. 2009;10:319-324. 4. Ortonne JP, Chimenti S, Reich K, et al. Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti-tumour necrosis factor agents: subanalysis of BELIEVE. J Eur Acad Dermatol Venereol. 2011;25:1012-1020. 5. Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118-128. 6. Piaserico S, Cazzaniga S, Chimenti S, et al. Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: results from the Italian Psocare registry. J Am Acad Dermatol. 2014;70:257-262.e3. http://dx.doi.org/10.1016/j.jaad.2015.08.030
Adalimumab drug survival in patients with psoriasis, Crohn’s disease, and rheumatoid arthritis: Relevant differences using the same treatment To the Editor: Adalimumab is approved for the treatment of immune mediated diseases (IMIDs) such as plaque psoriasis (PP), Crohn’s disease (CD), and rheumatoid arthritis (RA).1 Drug survival (DS) is used to analyze the time that patients remain on a specific drug. It is a composite measure of treatment success related to effectiveness, safety, and treatment satisfaction.2-4 Assumptions are frequently made that results from one IMID are also applicable to others. Consequently, dermatologists adopt the available results and knowledge of for instance rheumatologists to their own patients without knowing if this is correct. With this study, we aimed to compare DS and explain why DS differs between the 3 IMIDs.
176 Letters
JANUARY 2016
2. Coloe J, Morrell DS. Could higher doses of isotretinoin reduce the frequency of treatment failure in acne patients? J Am Acad Dermatol. 2011;65(2):422-423. 3. Blasiak RC, Stamey CR, Burkhart CN, et al. High-dose isotretinoin treatment and rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149(12): 1392-1398. 4. Absorica (isotretinoin) [ prescribing information]. Jacksonville, FL: Ranbaxy Laboratories Inc; 2014. 5. Gerhardstein PC, Hsu S, Liu A, et al. Relapse of acne following isotretinoin treatment: a retrospective study of 405 patients. J Drugs Dermatol. 2008;7(10):963. http://dx.doi.org/10.1016/j.jaad.2015.08.012
Effectiveness of sequential use of biologics in the treatment of moderate to severe psoriasis in real world Canadian academic clinical practice: A cohort study To the Editor: Biological agents are effective therapies for moderate to severe psoriasis.1 However, considerable variation in treatment response is observed in clinical practice,2 reflecting clinical and genetic heterogeneity of the disease as well as individual differences in drug metabolism and response, and suggesting that failure of 1 biologic does not preclude response to another biologic. In this large, multicenter study, we examine the effectiveness of adalimumab, etanercept, infliximab, and ustekinumab, and predictors of response to these treatments in patients with moderate to severe psoriasis following previous exposure to at least 1 biologic. Adult patients with psoriasis who failed treatment with at least 1 of the 4 biologics, defined as lack or loss of PASI 75 response/ physician global assessment (PGA) of 0 or 1 (clear and minimal disease, respectively) after $12 weeks of treatment, and then received another 1 of the 4 agents were included. Patients were treated at academic hospitals in Toronto, Ontario, Canada, between 2005 and 2014, and were followed up by the same dermatologist at every visit. Ethics approval was obtained. The number of psoriasis patients who achieved a significant response, defined as PASI 75 or PGA of 0 or 1 with at least 12 weeks of biologic therapy after previous biologic exposure, was quantified. Logistic regression was performed to determine potential predictors of treatment response using SAS version 9.3. Statistical significance was set as a 2-tailed P # .05. A total of 155 patients were included (Table I). A majority of patients who previously failed anti-tumor necrosis factor (TNF) therapy had a significant response to another anti-TNF or ustekinumab. Three of the 8 patients who failed ustekinumab therapy had a significant response to etanercept (Table II).
Table I. Clinical and demographic details: Baseline clinical and demographic data on 155 patients who were prescribed a tumor necrosis factor antagonist or ustekinumab and then switched to another biologic after treatment failure Variable
Median age in yr (IQR) Gender (N, %) Male Female Median disease duration in yrs (IQR) Comorbidities (N, % total) Psoriatic arthritis Inflammatory bowel disease Hypertension Dyslipidemia Diabetes Stroke Myocardial infarction Failed systemic therapies (N, % total) Methotrexate Acitretin Cyclosporine Phototherapy Baseline biologic (N, % total) Etanercept Adalimumab Infliximab Ustekinumab
Value
48.5 (19) 72/155 (46%) 83/155 (54%) 17.2 (15.0) 81/155 5/155 35/155 25/155 21/155 1/155 3/155
(52%) (3%) (22%) (16%) (13%) (1%) (2%)
98/155 50/155 34/155 109/155
(63%) (32%) (22%) (70%)
93/155 31/155 23/155 8/155
(60%) (20%) (15%) (5%)
IQR, Interquartile range; N, number of subjects meeting criteria.
Patients with 2 previously failed biologics were half as likely to respond to the present treatment compared to subjects with just 1 failed biologic (odds ratio: 0.474, 95% CI: 0.23-0.96, P ¼ .04). In patients who previously failed only 1 biologic, 45/75 (60%) of those who tried a different TNF antagonist and 36 of 43 (84%) of those who received ustekinumab achieved a significant response after 12 weeks of subsequent biologic therapy. In patients who previously failed 2 biologics, 4 of 8 (50%) of those who received another anti-TNF, and 11 of 22 (50%) of those who were given ustekinumab achieved clinically significant improvement. Of the 7 patients who previously failed 3 biologics, 4 of 7 (43%) achieved a significant improvement on another anti-TNF. Our results corroborate previously published findings of 65% efficacy, as defined by PASI 75 response, for etanercept,3 61% to 68% efficacy for adalimumab,4 and 66% for ustekinumab5 after these patients had failed at least 1 previous biologic. A recent study showed that in 105 patients who switched from a first to a second anti-TNF, a PASI 75 response was reached by 29% after 16 weeks and by 45.6% after 24 weeks.6 Differences in study design
J AM ACAD DERMATOL
Letters 177
VOLUME 74, NUMBER 1
Table II. Response rates of biologics among psoriasis patients with previous biologic exposure: Number and percentage of biologic-experienced patients who achieved significant improvement as defined by PASI 75 or PGA of 0 or 1 (clear and minimal disease, respectively) after 12 weeks of etanercept, infliximab, adalimumab, or ustekinumab New biologic (N = 155) Baseline biologic (n = 155) Etanercept (n = 23) Infliximab (n = 17) Adalimumab (n = 50) Ustekinumab (n = 65) Any anti-TNF (n = 90)
Etanercept (n = 93) Infliximab (n = 23) Adalimumab (n = 31) Ustekinumab (n = 8) Any anti-TNF (n = 147)
N/A 3/4 (75%) 7/11 (64%) 3/8 (38%) N/A
7/12 (58%) N/A 3/5 (60%) N/A N/A
24/43 (56%) 4/7 (57%) N/A N/A N/A
27/38 (71%) 9/12 (75%) 11/15 (73%) N/A 47/65 (72%)
31/55 7/11 10/16 3/8 48/82
(56%) (64%) (63%) (38%) (59%)
NA, Not applicable; TNF, tumor necrosis factor.
and patient populations should be considered when making comparisons. A significant improvement was defined as either PASI 75 response or PGA of 0 or 1 in this study, whereas the previous study only used PASI 75. A major limitation is the retrospective nature of this study. Another limitation may be that treatments were not completely standardized, randomized, or blinded. However, the data presented here came from ‘‘real world’’ clinical practice, thus rendering this study a valuable addition to the relatively limited literature on this topic. In summary, our results suggest that after failure of 1 anti-TNF, most patients are still likely to respond well to another biologic. Judy K. Qiang, BA,a Ali Shahbaz, BSc,b Whan Kim, BSc,c Joseph Marinas, BSc,c Simon Greaves, MSc,d and Jensen Yeung, MDe Faculty of Medicine,a University of Toronto; School of Medicine,b University of Ottawa, Ottawa; Michael G. DeGroote School of Medicine,c McMaster University, Hamilton; Dalla Lana School of Public Health,d University of Toronto, and Divison of Dermatology,e Department of Medicine, University of Toronto, Ontario, Canada. Funding source: None. Conflicts of interest: Dr Yeung serves as a speaker, consultant and investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, Janssen, Leo, Medimmune, Novartis, Pfizer, and Takeda. The other authors have no conflicts of interest to declare. Correspondence to: Dr Jensen Yeung, MD, Division of Dermatology, University of Toronto, 76 Grenville Street, 5th Floor, Toronto, ON, M5S 1B2, Canada E-mail: [email protected]
REFERENCES 1. Reich K, Nestle FO, Ortonne JP, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicenter, double-blind trial. Lancet. 2005; 366(9494):1367-1374. 2. Leman J, Burden AD. Sequential use of biologics in the treatment of moderate-to-severe plaque psoriasis. Br J Dermatol. 2012;167(Suppl 3):12-20. 3. Mazzotta A, Esposito M, Costanzo A, et al. Efficacy and safety of etanercept in psoriasis after switching from other treatments: an observational study. Am J Clin Dermatol. 2009;10:319-324. 4. Ortonne JP, Chimenti S, Reich K, et al. Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti-tumour necrosis factor agents: subanalysis of BELIEVE. J Eur Acad Dermatol Venereol. 2011;25:1012-1020. 5. Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118-128. 6. Piaserico S, Cazzaniga S, Chimenti S, et al. Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: results from the Italian Psocare registry. J Am Acad Dermatol. 2014;70:257-262.e3. http://dx.doi.org/10.1016/j.jaad.2015.08.030
Adalimumab drug survival in patients with psoriasis, Crohn’s disease, and rheumatoid arthritis: Relevant differences using the same treatment To the Editor: Adalimumab is approved for the treatment of immune mediated diseases (IMIDs) such as plaque psoriasis (PP), Crohn’s disease (CD), and rheumatoid arthritis (RA).1 Drug survival (DS) is used to analyze the time that patients remain on a specific drug. It is a composite measure of treatment success related to effectiveness, safety, and treatment satisfaction.2-4 Assumptions are frequently made that results from one IMID are also applicable to others. Consequently, dermatologists adopt the available results and knowledge of for instance rheumatologists to their own patients without knowing if this is correct. With this study, we aimed to compare DS and explain why DS differs between the 3 IMIDs.