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Review

Adalimumab effect on pain in hidradenitis suppurativa patients: systematic review and meta-analysis

Author Affiliation(s)

Abstract

Introduction: Pain is experienced by most patients with hidradenitis suppurativa (HS) and has a severe impact on their quality of life. Its management still presents a challenge. Adalimumab, a TNF-a antagonist, has shown promising results in HS-related pain reduction.


Objectives: To aggregate and synthesize all existing evidence regarding the effect of adalimumab on HS-associated skin pain.


Methods: We identified original controlled and uncontrolled studies with participants receiving adalimumab, which included change in pain score post-treatment comparing to baseline as an endpoint. We searched MEDLINE, ScienceDirect, the Cochrane Library, ClinicalTrials.gov and International Clinical Trials Registry Platform. The primary endpoint of our study was mean change (continuous variable) of pain scores at week 12 comparing to baseline.


Results: We performed a meta-analysis of four randomized controlled trials (282 patients in the intervention group and 266 patients in the control group). Adalimumab brought about a 0.418 reduction in mean pain score at its worst with 95%CI [-0.588, -0.248] and p = 0.000 at 12 weeks after treatment commencement. Four more studies were included in a qualitative synthesis, two of which reported statistically significant reduction in pain scores at week 12.

Conclusions: Adalimumab could be prescribed more readily in cases of hidradenitis associated with significant skin pain.


 


 

Keywords : hidradenitis suppurativa, adalimumab, pain, VAS, NRS30

References

References 1 Kurzen H, Kurokawa I, Jemec GBE, et al. What causes hidradenitis suppurativa? Exp Dermatol 2008; 17:455–6; discussion 457-72. 2 Kaaz K, Szepietowski JC, Matusiak Ł. Influence of itch and pain on sleep quality in patients with hidradenitis suppurativa. Acta Derm Venereol 2018; 98:757–61. 3 Nielsen RM, Lindsø Andersen P, Sigsgaard V, et al. Pain perception in patients with hidradenitis suppurativa. Br J Dermatol 2019; :bjd.17935. 4 Matusiak Ł, Szczęch J, Kaaz K, et al. Clinical Characteristics of Pruritus and Pain in Patients with Hidradenitis Suppurativa. Acta Derm Venereol 2018; 98:191–4. 5 Patel ZS, Hoffman LK, Buse DC, et al. Pain, Psychological Comorbidities, Disability, and Impaired Qualify of Life in Hidradenitis Suppurativa. Curr. Pain Headache Rep. 2017; 21. doi:10.1007/s11916-017-0647-3. 6 Chernyshov P V., Zouboulis CC, Tomas-Aragones L, et al. Quality of life measurement in hidradenitis suppurativa: position statement of the European Academy of Dermatology and Venereology task forces on Quality of Life and Patient-Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa. J Eur Acad Dermatology Venereol 2019; 33:1633–43. 7 Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatology Venereol 2015; 29:619–44. 8 Puza CJ, Wolfe SA, Jaleel T. Pain Management in Patients With Hidradenitis Suppurativa Requiring Surgery. Dermatologic Surg 2018; :1. 9 Horváth B, Janse IC, Sibbald GR. Pain management in patients with hidradenitis suppurativa. J Am Acad Dermatol 2015; 73:S47-51. 10 Ring HC, Theut Riis P, Miller IM, et al. Self-reported pain management in hidradenitis suppurativa. Br J Dermatol 2016; 174:909–11. 11 Ring HC, Sørensen H, Miller IM, et al. Pain in Hidradenitis Suppurativa: A Pilot Study. Acta Derm Venereol 2016; 96:554–6. 12 Jemec G. Quality of life considerations and pain management in hidradenitis suppurativa. Semin Cutan Med Surg 2017; 36:75–8. 13 Enamandram M, Rathmell JP, Kimball AB. Chronic pain management in dermatology Pharmacotherapy and therapeutic monitoring with opioid analgesia. J. Am. Acad. Dermatol. 2015; 73:575–82. 14 Scheinfeld N, Sundaram M, Teixeira H, et al. Reduction in pain scores and improvement in depressive symptoms in patients with hidradenitis suppurativa treated with adalimumab in a phase 2, randomized, placebo-controlled trial. Dermatol Online J 2016; 22. 15 Kimball AB, Sundaram M, Shields AL, et al. Adalimumab alleviates skin pain in patients with moderate-to-severe hidradenitis suppurativa: Secondary efficacy results from the PIONEER I and PIONEER II randomized controlled trials. J Am Acad Dermatol 2018; 79:1141–3. 16 Gupta AK, Studholme C. Adalimumab (Humira) for the Treatment of Hidradenitis Suppurativa. Skin Therapy Lett 2016; 21:1–4. 17 Haefeli M, Elfering A. Pain assessment. Eur. Spine J. 2006; 15:S17. 18 Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343. doi:10.1136/bmj.d5928. 19 Slim K, Nini E, Forestier D, et al. Methodological index for non-randomized studies (Minors): Development and validation of a new instrument. ANZ J Surg 2003; 73:712–6. 20 Study Quality Assessment Tools | NHLBI, NIH [WWW Document]. . 21 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; 157:846–55. 22 Ryan C, Sobell JM, Leonardi CL, et al. Safety of Adalimumab Dosed Every Week and Every Other Week: Focus on Patients with Hidradenitis Suppurativa or Psoriasis. Am J Clin Dermatol 2018; 19:437–47. 23 Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med 2016; 375:422–34. 24 Miller I, Lynggaard CD, Lophaven S, et al. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa. Br J Dermatol 2011; 165:391–8. 25 Amano M, Grant A, Kerdel FA. A prospective open-label clinical trial of adalimumab for the treatment of hidradenitis suppurativa. Int J Dermatol 2010; 49:950–5. 26 Morita A, Takahashi H, Ozawa K, et al. Twenty‐four‐week interim analysis from a phase 3 open‐label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa. J Dermatol 2019; 46:745–51. 27 Caposiena Caro RD, Cannizzaro M V., Tartaglia C, Bianchi L. Clinical response rate and flares of hidradenitis suppurativa in the treatment with adalimumab. Clin Exp Dermatol 2020; 45:438–44. 28 Post Marketing Observational Study ( PMOS ) to Assess Quality of Life in Swedish Hidradenitis Suppurativa ( HS ) Patients ( HOPE ). 2016. 29 Emtestam L, Al-Bayatti A, Popovich-Silwerfeldt K, Weyler L. Post marketing observational study to assess quality of life changes in Swedish Patients with moderate or severe Hidradenitis Suppurativa on Adalimumab Treatment (HOPE study), interim analysis. Exp Dermatol 2018; 27:16–7. 30 Kimball AB, Chen K, Okun M, Sundaram M. Adalimumab reduces pain in patients with hidradenitis suppurativa: Results from a placebo-controlled phase II trial. J Am Acad Dermatol 2012; 66:AB42. 31 Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol 2020. doi:10.1016/j.jaad.2020.09.039. 32 Krajewski P, Matusiak �, von Stebut E, et al. Pain in Hidradenitis Suppurativa: A Cross-sectional Study of 1,795 Patients. Acta Derm Venereol 2020; :0. 33 Ravn Jørgensen AH, Yao Y, Thomsen SF, Christian Ring H. Métodos referidos por los pacientes para aliviar el dolor asociado a la Hidradenitis Supurativa. Actas Dermosifiliogr 2020. doi:10.1016/j.ad.2020.08.011. 34 Gulliver W, Zouboulis CC, Prens E, et al. Evidence-based approach to the treatment of hidradenitis suppurativa/acne inversa, based on the European guidelines for hidradenitis suppurativa. Rev Endocr Metab Disord 2016; 17:343–51. 35 Fotiadou C, Vakirlis E, Ioannides D. Spotlight on adalimumab in the treatment of active moderate-to-severe hidradenitis suppurativa. Clin Cosmet Investig Dermatol 2016; 9:367–72. 36 Thorlacius L, Theut Riis P, Jemec GBE. Severe hidradenitis suppurativa responding to treatment with secukinumab: a case report. Br J Dermatol 2018; 179:182–5. 37 Blok JL, Li K, Brodmerkel C, et al. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol 2016; 174:839–46. 38 Weber P, Seyed Jafari SM, Yawalkar N, Hunger RE. Apremilast in the treatment of moderate to severe hidradenitis suppurativa: A case series of 9 patients. J Am Acad Dermatol 2017; 76:1189–91. 39 Zouboulis CC. Pain Index: a new prospective hidradenitis suppurativa patient-reported outcome measure instrument. Br. J. Dermatol. 2021. doi:10.1111/bjd.19798. References 1 Kurzen H, Kurokawa I, Jemec GBE, et al. What causes hidradenitis suppurativa? Exp Dermatol 2008; 17:455–6; discussion 457-72. 2 Kaaz K, Szepietowski JC, Matusiak Ł. Influence of itch and pain on sleep quality in patients with hidradenitis suppurativa. Acta Derm Venereol 2018; 98:757–61. 3 Nielsen RM, Lindsø Andersen P, Sigsgaard V, et al. Pain perception in patients with hidradenitis suppurativa. Br J Dermatol 2019; :bjd.17935. 4 Matusiak Ł, Szczęch J, Kaaz K, et al. Clinical Characteristics of Pruritus and Pain in Patients with Hidradenitis Suppurativa. Acta Derm Venereol 2018; 98:191–4. 5 Patel ZS, Hoffman LK, Buse DC, et al. Pain, Psychological Comorbidities, Disability, and Impaired Qualify of Life in Hidradenitis Suppurativa. Curr. Pain Headache Rep. 2017; 21. doi:10.1007/s11916-017-0647-3. 6 Chernyshov P V., Zouboulis CC, Tomas-Aragones L, et al. Quality of life measurement in hidradenitis suppurativa: position statement of the European Academy of Dermatology and Venereology task forces on Quality of Life and Patient-Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa. J Eur Acad Dermatology Venereol 2019; 33:1633–43. 7 Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatology Venereol 2015; 29:619–44. 8 Puza CJ, Wolfe SA, Jaleel T. Pain Management in Patients With Hidradenitis Suppurativa Requiring Surgery. Dermatologic Surg 2018; :1. 9 Horváth B, Janse IC, Sibbald GR. Pain management in patients with hidradenitis suppurativa. J Am Acad Dermatol 2015; 73:S47-51. 10 Ring HC, Theut Riis P, Miller IM, et al. Self-reported pain management in hidradenitis suppurativa. Br J Dermatol 2016; 174:909–11. 11 Ring HC, Sørensen H, Miller IM, et al. Pain in Hidradenitis Suppurativa: A Pilot Study. Acta Derm Venereol 2016; 96:554–6. 12 Jemec G. Quality of life considerations and pain management in hidradenitis suppurativa. Semin Cutan Med Surg 2017; 36:75–8. 13 Enamandram M, Rathmell JP, Kimball AB. Chronic pain management in dermatology Pharmacotherapy and therapeutic monitoring with opioid analgesia. J. Am. Acad. Dermatol. 2015; 73:575–82. 14 Scheinfeld N, Sundaram M, Teixeira H, et al. Reduction in pain scores and improvement in depressive symptoms in patients with hidradenitis suppurativa treated with adalimumab in a phase 2, randomized, placebo-controlled trial. Dermatol Online J 2016; 22. 15 Kimball AB, Sundaram M, Shields AL, et al. Adalimumab alleviates skin pain in patients with moderate-to-severe hidradenitis suppurativa: Secondary efficacy results from the PIONEER I and PIONEER II randomized controlled trials. J Am Acad Dermatol 2018; 79:1141–3. 16 Gupta AK, Studholme C. Adalimumab (Humira) for the Treatment of Hidradenitis Suppurativa. Skin Therapy Lett 2016; 21:1–4. 17 Haefeli M, Elfering A. Pain assessment. Eur. Spine J. 2006; 15:S17. 18 Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343. doi:10.1136/bmj.d5928. 19 Slim K, Nini E, Forestier D, et al. Methodological index for non-randomized studies (Minors): Development and validation of a new instrument. ANZ J Surg 2003; 73:712–6. 20 Study Quality Assessment Tools | NHLBI, NIH [WWW Document]. . 21 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; 157:846–55. 22 Ryan C, Sobell JM, Leonardi CL, et al. Safety of Adalimumab Dosed Every Week and Every Other Week: Focus on Patients with Hidradenitis Suppurativa or Psoriasis. Am J Clin Dermatol 2018; 19:437–47. 23 Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med 2016; 375:422–34. 24 Miller I, Lynggaard CD, Lophaven S, et al. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa. Br J Dermatol 2011; 165:391–8. 25 Amano M, Grant A, Kerdel FA. A prospective open-label clinical trial of adalimumab for the treatment of hidradenitis suppurativa. Int J Dermatol 2010; 49:950–5. 26 Morita A, Takahashi H, Ozawa K, et al. Twenty‐four‐week interim analysis from a phase 3 open‐label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa. J Dermatol 2019; 46:745–51. 27 Caposiena Caro RD, Cannizzaro M V., Tartaglia C, Bianchi L. Clinical response rate and flares of hidradenitis suppurativa in the treatment with adalimumab. Clin Exp Dermatol 2020; 45:438–44. 28 Post Marketing Observational Study ( PMOS ) to Assess Quality of Life in Swedish Hidradenitis Suppurativa ( HS ) Patients ( HOPE ). 2016. 29 Emtestam L, Al-Bayatti A, Popovich-Silwerfeldt K, Weyler L. Post marketing observational study to assess quality of life changes in Swedish Patients with moderate or severe Hidradenitis Suppurativa on Adalimumab Treatment (HOPE study), interim analysis. Exp Dermatol 2018; 27:16–7. 30 Kimball AB, Chen K, Okun M, Sundaram M. Adalimumab reduces pain in patients with hidradenitis suppurativa: Results from a placebo-controlled phase II trial. J Am Acad Dermatol 2012; 66:AB42. 31 Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol 2020. doi:10.1016/j.jaad.2020.09.039. 32 Krajewski P, Matusiak �, von Stebut E, et al. Pain in Hidradenitis Suppurativa: A Cross-sectional Study of 1,795 Patients. Acta Derm Venereol 2020; :0. 33 Ravn Jørgensen AH, Yao Y, Thomsen SF, Christian Ring H. Métodos referidos por los pacientes para aliviar el dolor asociado a la Hidradenitis Supurativa. Actas Dermosifiliogr 2020. doi:10.1016/j.ad.2020.08.011. 34 Gulliver W, Zouboulis CC, Prens E, et al. Evidence-based approach to the treatment of hidradenitis suppurativa/acne inversa, based on the European guidelines for hidradenitis suppurativa. Rev Endocr Metab Disord 2016; 17:343–51. 35 Fotiadou C, Vakirlis E, Ioannides D. Spotlight on adalimumab in the treatment of active moderate-to-severe hidradenitis suppurativa. Clin Cosmet Investig Dermatol 2016; 9:367–72. 36 Thorlacius L, Theut Riis P, Jemec GBE. Severe hidradenitis suppurativa responding to treatment with secukinumab: a case report. Br J Dermatol 2018; 179:182–5. 37 Blok JL, Li K, Brodmerkel C, et al. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br J Dermatol 2016; 174:839–46. 38 Weber P, Seyed Jafari SM, Yawalkar N, Hunger RE. Apremilast in the treatment of moderate to severe hidradenitis suppurativa: A case series of 9 patients. J Am Acad Dermatol 2017; 76:1189–91. 39 Zouboulis CC. Pain Index: a new prospective hidradenitis suppurativa patient-reported outcome measure instrument. Br. J. Dermatol. 2021. doi:10.1111/bjd.19798.

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