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Erschienen in: American Journal of Clinical Dermatology 2/2021

26.11.2020 | Original Research Article

Therapeutic Drug Monitoring in Patients with Suboptimal Response to Adalimumab for Hidradenitis Suppurativa: A Retrospective Case Series

verfasst von: Tasnim Abdalla, Mark Mansour, Dorra Bouazzi, Michelle A. Lowes, Gregor B. E. Jemec, Afsaneh Alavi

Erschienen in: American Journal of Clinical Dermatology | Ausgabe 2/2021

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Abstract

Background

Adalimumab, a tumor necrosis factor-α inhibitor, is a biologic used for the treatment of moderate-to-severe hidradenitis suppurativa (HS). It is well known that patients may experience loss of efficacy from its use in other conditions, and it is suggested that developing a strategy for therapeutic drug monitoring (TDM) may help secure optimal clinical outcomes.

Objectives

We sought to determine serum adalimumab concentrations and anti-adalimumab antibody (AAA) status in patients with moderate-to-severe HS.

Methods

A retrospective case series of 38 patients with suboptimal response to adalimumab 40 mg weekly was conducted at a community dermatology clinic. Adalimumab serum trough levels, AAA status, and inflammatory biomarkers were collected. Blood was drawn on identification of suboptimal response (after a minimum of 12 weeks) and was collected once prior to receiving the next scheduled dose. Kruskal–Wallis and Chi-squared tests were used for data analysis.

Results

A total of 38 patients had a median adalimumab trough concentration of 8.76 (interquartile range [IQR] 1.3–12.5) µg/mL. The median duration of adalimumab therapy of all patients was 21 (IQR 12–24) months. AAAs were detected in nine patients (24%), and all had subtherapeutic serum concentrations (< 6 µg/mL). Patients who were AAA+ had a significantly lower median adalimumab concentration than those who were AAA− (0.02 µg/mL [range 0.02–0.81] vs. 10.14 [range 0.76–48.00]; p = 0.0006).

Conclusion

Patients with AAAs had significantly lower serum adalimumab levels. The current study suggests that TDM may identify underlying reasons for suboptimal response and detect patients who may benefit from dose optimization strategies.
Literatur
2.
Zurück zum Zitat Orenstein LAV, Nguyen TV, Damiani G, Sayed C, Jemec GBE, Hamzavi I. Medical and surgical management of hidradenitis suppurativa: a review of international treatment guidelines and implementation in general dermatology practice. Dermatology. 2020;236(5):393–412.CrossRef Orenstein LAV, Nguyen TV, Damiani G, Sayed C, Jemec GBE, Hamzavi I. Medical and surgical management of hidradenitis suppurativa: a review of international treatment guidelines and implementation in general dermatology practice. Dermatology. 2020;236(5):393–412.CrossRef
4.
Zurück zum Zitat Kimball AB, Kerdel F, Adams D, et al. Adalimumab for the treatment of moderate to severe Hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012;157(12):846–55.CrossRef Kimball AB, Kerdel F, Adams D, et al. Adalimumab for the treatment of moderate to severe Hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012;157(12):846–55.CrossRef
5.
Zurück zum Zitat Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375(5):422–34.CrossRef Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375(5):422–34.CrossRef
6.
Zurück zum Zitat Kimball AB, Sobell JM, Zouboulis CC, et al. HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study. J Eur Acad Dermatol Venereol. 2016;30(6):989–94.CrossRef Kimball AB, Sobell JM, Zouboulis CC, et al. HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study. J Eur Acad Dermatol Venereol. 2016;30(6):989–94.CrossRef
7.
Zurück zum Zitat Kimball AB, Jemec GBE, Yang M, et al. Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol. 2014;171(6):1434–42.CrossRef Kimball AB, Jemec GBE, Yang M, et al. Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol. 2014;171(6):1434–42.CrossRef
8.
Zurück zum Zitat Zouboulis CC, Okun MM, Prens EP, et al. Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa/acne inversa: 3-year results of a phase 3 open-label extension study. J Am Acad Dermatol. 2019;80(1):60-69.e2.CrossRef Zouboulis CC, Okun MM, Prens EP, et al. Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa/acne inversa: 3-year results of a phase 3 open-label extension study. J Am Acad Dermatol. 2019;80(1):60-69.e2.CrossRef
9.
Zurück zum Zitat Jemec GBE, Okun MM, Forman SB, et al. Adalimumab medium-term dosing strategy in moderate-to-severe hidradenitis suppurativa: integrated results from the phase III randomized placebo-controlled PIONEER trials. Br J Dermatol. 2019;181(5):967–75.CrossRef Jemec GBE, Okun MM, Forman SB, et al. Adalimumab medium-term dosing strategy in moderate-to-severe hidradenitis suppurativa: integrated results from the phase III randomized placebo-controlled PIONEER trials. Br J Dermatol. 2019;181(5):967–75.CrossRef
11.
Zurück zum Zitat Jemec GBE. Predicting response to anti-TNF-alpha treatment in Hidradenitis suppurativa. Br J Dermatol. 2013;168(2):233.CrossRef Jemec GBE. Predicting response to anti-TNF-alpha treatment in Hidradenitis suppurativa. Br J Dermatol. 2013;168(2):233.CrossRef
12.
Zurück zum Zitat Lombardi G, Perego S, Sansoni V, et al. Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence. BMJ Open. 2016;6(12):e011941.CrossRef Lombardi G, Perego S, Sansoni V, et al. Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence. BMJ Open. 2016;6(12):e011941.CrossRef
13.
Zurück zum Zitat Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):921–6.CrossRef Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):921–6.CrossRef
14.
Zurück zum Zitat Hoxha A, Calligaro A, Tonello M, et al. The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: a prospective multicentre study. Jt Bone Spine. 2016;83(2):167–71.CrossRef Hoxha A, Calligaro A, Tonello M, et al. The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: a prospective multicentre study. Jt Bone Spine. 2016;83(2):167–71.CrossRef
15.
Zurück zum Zitat Ungar B, Engel T, Yablecovitch D, et al. Prospective observational evaluation of time-dependency of adalimumab immunogenicity and drug concentrations: the POETIC study. Am J Gastroenterol. 2018;113(6):890–8.CrossRef Ungar B, Engel T, Yablecovitch D, et al. Prospective observational evaluation of time-dependency of adalimumab immunogenicity and drug concentrations: the POETIC study. Am J Gastroenterol. 2018;113(6):890–8.CrossRef
16.
Zurück zum Zitat Nakase H, Motoya S, Matsumoto T, et al. Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn’s disease: a subanalysis of the DIAMOND trial. Aliment Pharmacol Ther. 2017;46(9):873–82.CrossRef Nakase H, Motoya S, Matsumoto T, et al. Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn’s disease: a subanalysis of the DIAMOND trial. Aliment Pharmacol Ther. 2017;46(9):873–82.CrossRef
17.
Zurück zum Zitat Nader A, Beck D, Noertersheuser P, et al. Population pharmacokinetics and immunogenicity of adalimumab in adult patients with moderate-to-severe hidradenitis suppurativa. Clin Pharmacokinet. 2017;56(9):1091–102.CrossRef Nader A, Beck D, Noertersheuser P, et al. Population pharmacokinetics and immunogenicity of adalimumab in adult patients with moderate-to-severe hidradenitis suppurativa. Clin Pharmacokinet. 2017;56(9):1091–102.CrossRef
20.
Zurück zum Zitat Feuerstein JD, Nguyen GC, Kupfer SS, et al. American gastroenterological association institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017;153(3):827–34.CrossRef Feuerstein JD, Nguyen GC, Kupfer SS, et al. American gastroenterological association institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017;153(3):827–34.CrossRef
21.
Zurück zum Zitat Zouboulis CC, Bechara FG, Dickinson-Blok JL, et al. Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization—systematic review and recommendations from the HS ALLIANCE working group. J Eur Acad Dermatol Venereol. 2019;33(1):19–31.CrossRef Zouboulis CC, Bechara FG, Dickinson-Blok JL, et al. Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization—systematic review and recommendations from the HS ALLIANCE working group. J Eur Acad Dermatol Venereol. 2019;33(1):19–31.CrossRef
22.
Zurück zum Zitat Bykerk VP, Akhavan P, Hazlewood GS, et al. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol. 2012;39(8):1559–82.CrossRef Bykerk VP, Akhavan P, Hazlewood GS, et al. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol. 2012;39(8):1559–82.CrossRef
23.
Zurück zum Zitat Zouboulis CC, Hansen H, Caposiena Caro RD, et al. Adalimumab dose intensification in recalcitrant hidradenitis suppurativa/acne inversa. DRM. 2019;18:1–6. Zouboulis CC, Hansen H, Caposiena Caro RD, et al. Adalimumab dose intensification in recalcitrant hidradenitis suppurativa/acne inversa. DRM. 2019;18:1–6.
24.
Zurück zum Zitat Karmiris K, Paintaud G, Noman M, et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology. 2009;137(5):1628–40.CrossRef Karmiris K, Paintaud G, Noman M, et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology. 2009;137(5):1628–40.CrossRef
25.
Zurück zum Zitat Papamichael K, Juncadella A, Wong D, et al. Proactive therapeutic drug monitoring of adalimumab is associated with better long-term outcomes compared with standard of care in patients with inflammatory bowel disease. J Crohns Colitis. 2019;13(8):976–81.CrossRef Papamichael K, Juncadella A, Wong D, et al. Proactive therapeutic drug monitoring of adalimumab is associated with better long-term outcomes compared with standard of care in patients with inflammatory bowel disease. J Crohns Colitis. 2019;13(8):976–81.CrossRef
26.
Zurück zum Zitat Bartelds GM, Krieckaert CLM, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305(14):1460–8.CrossRef Bartelds GM, Krieckaert CLM, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305(14):1460–8.CrossRef
27.
Zurück zum Zitat Zittan E, Kabakchiev B, Milgrom R, et al. Higher adalimumab drug levels are associated with mucosal healing in patients with Crohn’s disease. J Crohns Colitis. 2016;10(5):510–5.CrossRef Zittan E, Kabakchiev B, Milgrom R, et al. Higher adalimumab drug levels are associated with mucosal healing in patients with Crohn’s disease. J Crohns Colitis. 2016;10(5):510–5.CrossRef
28.
Zurück zum Zitat Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320-1329.e3.CrossRef Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320-1329.e3.CrossRef
29.
Zurück zum Zitat Mazor Y, Almog R, Kopylov U, et al. Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn’s disease. Aliment Pharmacol Ther. 2014;40(6):620–8.CrossRef Mazor Y, Almog R, Kopylov U, et al. Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn’s disease. Aliment Pharmacol Ther. 2014;40(6):620–8.CrossRef
30.
Zurück zum Zitat Mitrev N, Casteele NV, Seow CH, et al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017;46(11–12):1037–53.CrossRef Mitrev N, Casteele NV, Seow CH, et al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017;46(11–12):1037–53.CrossRef
31.
Zurück zum Zitat Ben-Horin S, Chowers Y. Tailoring anti-TNF therapy in IBD: drug levels and disease activity. Nat Rev Gastroenterol Hepatol. 2014;11(4):243–55.CrossRef Ben-Horin S, Chowers Y. Tailoring anti-TNF therapy in IBD: drug levels and disease activity. Nat Rev Gastroenterol Hepatol. 2014;11(4):243–55.CrossRef
32.
Zurück zum Zitat Steenholdt C, Bendtzen K, Brynskov J, et al. Optimizing treatment with TNF inhibitors in inflammatory bowel disease by monitoring drug levels and antidrug antibodies. Inflamm Bowel Dis. 2016;22(8):1999–2015.CrossRef Steenholdt C, Bendtzen K, Brynskov J, et al. Optimizing treatment with TNF inhibitors in inflammatory bowel disease by monitoring drug levels and antidrug antibodies. Inflamm Bowel Dis. 2016;22(8):1999–2015.CrossRef
33.
Zurück zum Zitat Ben-Horin S, Waterman M, Kopylov U, et al. Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(4):444–7.CrossRef Ben-Horin S, Waterman M, Kopylov U, et al. Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(4):444–7.CrossRef
34.
Zurück zum Zitat Ungar B, Kopylov U, Engel T, et al. Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab. Aliment Pharmacol Ther. 2017;45(2):276–82.CrossRef Ungar B, Kopylov U, Engel T, et al. Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab. Aliment Pharmacol Ther. 2017;45(2):276–82.CrossRef
35.
Zurück zum Zitat Bressler B, Marshall JK, Bernstein CN, et al. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus. Gastroenterology. 2015;148(5):1035-1058.e3.CrossRef Bressler B, Marshall JK, Bernstein CN, et al. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus. Gastroenterology. 2015;148(5):1035-1058.e3.CrossRef
36.
Zurück zum Zitat Garcês S, Demengeot J, Benito-Garcia E. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis. 2013;72(12):1947–55.CrossRef Garcês S, Demengeot J, Benito-Garcia E. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis. 2013;72(12):1947–55.CrossRef
37.
Zurück zum Zitat Doeleman MJH, van Maarseveen EM, Swart JF. Immunogenicity of biologic agents in juvenile idiopathic arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2019;58(10):1839–49.CrossRef Doeleman MJH, van Maarseveen EM, Swart JF. Immunogenicity of biologic agents in juvenile idiopathic arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2019;58(10):1839–49.CrossRef
39.
Zurück zum Zitat Zisapel M, Zisman D, Madar-Balakirski N, et al. Prevalence of TNF-α blocker immunogenicity in psoriatic arthritis. J Rheumatol. 2015;42(1):73–8.CrossRef Zisapel M, Zisman D, Madar-Balakirski N, et al. Prevalence of TNF-α blocker immunogenicity in psoriatic arthritis. J Rheumatol. 2015;42(1):73–8.CrossRef
40.
Zurück zum Zitat Ingram JR, Collier F, Brown D, et al. British Association of Dermatologists guidelines for the management of hidradenitis suppurativa (acne inversa) 2018. Br J Dermatol. 2019;180(5):1009–17.CrossRef Ingram JR, Collier F, Brown D, et al. British Association of Dermatologists guidelines for the management of hidradenitis suppurativa (acne inversa) 2018. Br J Dermatol. 2019;180(5):1009–17.CrossRef
41.
Zurück zum Zitat Wang LL, Micheletti RG. Low-dose methotrexate as rescue therapy in patients with hidradenitis suppurativa and pyoderma gangrenosum developing human antichimeric antibodies to infliximab: a retrospective chart review. J Am Acad Dermatol. 2020;82(2):507–10.CrossRef Wang LL, Micheletti RG. Low-dose methotrexate as rescue therapy in patients with hidradenitis suppurativa and pyoderma gangrenosum developing human antichimeric antibodies to infliximab: a retrospective chart review. J Am Acad Dermatol. 2020;82(2):507–10.CrossRef
42.
Zurück zum Zitat Savage KT, Flood KS, Porter ML, et al. TNF-α inhibitors in the treatment of hidradenitis suppurativa. Ther Adv Chronic Dis. 2019;1(10):1–12. Savage KT, Flood KS, Porter ML, et al. TNF-α inhibitors in the treatment of hidradenitis suppurativa. Ther Adv Chronic Dis. 2019;1(10):1–12.
43.
Zurück zum Zitat McPhie ML, Bridgman AC, Kirchhof MG. Combination therapies for hidradenitis suppurativa: a retrospective chart review of 31 patients. J Cutan Med Surg. 2019;23(3):270–6.CrossRef McPhie ML, Bridgman AC, Kirchhof MG. Combination therapies for hidradenitis suppurativa: a retrospective chart review of 31 patients. J Cutan Med Surg. 2019;23(3):270–6.CrossRef
44.
Zurück zum Zitat Kennedy NA, Heap GA, Green HD, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol. 2019;4(5):341–53.CrossRef Kennedy NA, Heap GA, Green HD, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol. 2019;4(5):341–53.CrossRef
45.
Zurück zum Zitat Atiqi S, Hooijberg F, Loeff FC, Rispens T, Wolbink GJ. Immunogenicity of TNF-Inhibitors. Front Immunol. 2020;26(11):312.CrossRef Atiqi S, Hooijberg F, Loeff FC, Rispens T, Wolbink GJ. Immunogenicity of TNF-Inhibitors. Front Immunol. 2020;26(11):312.CrossRef
Metadaten
Titel
Therapeutic Drug Monitoring in Patients with Suboptimal Response to Adalimumab for Hidradenitis Suppurativa: A Retrospective Case Series
verfasst von
Tasnim Abdalla
Mark Mansour
Dorra Bouazzi
Michelle A. Lowes
Gregor B. E. Jemec
Afsaneh Alavi
Publikationsdatum
26.11.2020
Verlag
Springer International Publishing
Erschienen in
American Journal of Clinical Dermatology / Ausgabe 2/2021
Print ISSN: 1175-0561
Elektronische ISSN: 1179-1888
DOI
https://doi.org/10.1007/s40257-020-00575-3

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