Treatment of hidradenitis suppurativa with biologic medications

Treatment of hidradenitis suppurativa with biologic medications Robert A. Lee, MD, PhD,a and Daniel B. Eisen, MDb San Diego and Sacramento, California Given the absence of significant improvement in the treatment of hidradenitis suppurativa (HS) with traditional medical and surgical therapies, biologics have piqued the interest of research investigators. The efficacy of biologics in the treatment of inflammatory conditions like psoriasis and rheumatoid arthritis is well-documented. More recently, success with biologics has been demonstrated in atopic dermatitis, another dermatological condition associated with inflammatory states. Researchers have begun to probe the utility of biologic agents in less prevalent conditions that feature inflammation as a key characteristic, namely, hidradenitis suppurativa. Five agents in particular adalimumab, anakinra, etanercept, infliximab, and ustekinumab, have been explored in the setting of HS. Results to date put forward adalimumab and infliximab as biologic treatments that can safely be initiated with some expectant efficacy. Other biologic agents require more rigorous examination before they are worthy of addition to the treatment armamentarium. ( J Am Acad Dermatol 2015;73:S82-8.) Key words: acne inversa; adalimumab; anakinra; biologics; etanercept; hidradenitis suppurativa; infliximab; treatment; tumor necrosis factorealfa; ustekinumab.

INTRODUCTION Biologic medications—proteins derived from human genes—have been used to treat inflammatory diseases, such as rheumatoid arthritis and psoriasis, for decades. Preliminary success in the management of those conditions served as the impetus to explore the role of biologics in treating other disorders of an inflammatory nature, such as hidradenitis suppurativa (HS). Though the list of biologic medications has lengthened in recent years, most published results on their use in the setting of HS are based on 5 medications: adalimumab, anakinra, etanercept, infliximab, and ustekinumab. This review will focus primarily on these medications (Table I).1 Etanercept Etanercept is a fully humanized fusion protein composed of the tumor necrosis factorealfa (TNFa) receptor and receptor protein component of immunoglobulin G1. This protein binds to transmembrane TNFa but unlike infliximab does not bind to soluble TNFa.2 From the Dermatology Clinic,a University of California San Diego, and the Department of Dermatology,b University of California Davis, Sacramento. This publication was supported through funding provided by AbbVie Corporation. Disclosure: Dr Lee is an investigator for AbbVie and Astra Zeneca. Dr Eisen has no conflicts to declare. Accepted for publication July 16, 2015.

S82

Several cohort studies have been conducted on the use of etanercept for patients with HS. Three of these demonstrated mainly positive results.3-5 Cusack et al3 found a 61% reduction in disease activity in their open-label study. GiamarellosBourboulis et al4 found that 6 of 10 patients had a significant reduction in their visual analog scale scores, while Sotiriou et al5 described mean improvement of 68.8% and 66.5% in Dermatology Life Quality Index (DLQI) scores. Lee et al6 did not confirm these promising results, with just 3 of 15 patients improving. Only 1 randomized, double-blind trial has been reported to date on the use of etanercept for HS.7 Patients were enrolled to receive either a 50-mg biweekly injection of the biologic or placebo, with no significant differences uncovered between etanercept and placebo after 12 weeks of treatment, as measured by the primary endpoint (Physician Global Assessment) and secondary endpoints (Patient Global Assessment or DLQI). Similarly, a recent systematic review on the use of TNFa inhibitors found that etanercept was not Correspondence to: Robert A. Lee, MD, PhD, University of California San Diego, Dermatology Clinic, 8899 University Center Ln, Ste 350, San Diego, CA 92122. E-mail: [email protected]. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.07.053

J AM ACAD DERMATOL

Lee and Eisen S83

VOLUME 73, NUMBER 5

associated with an improvement in the DLQI.8 Though the data are not favorable regarding the use of etanercept in the treatment of HS, trials have enrolled relatively few patients, making any conclusions regarding its place in the treatment armamentarium premature. The availability of larger datasets would provide insight into its efficiency.

80 mg at week 0 and of 40 mg every second week), patients with HS treated for 3 months experienced significant improvement that was detected as early as 2 weeks after initiation, but the biologic failed to demonstrate significant efficacy at week 12.2,10 In another prospective, randomized, double-blind, placebo-controlled study of adalimumab treatment (a subcutaneous dose of Infliximab 40 mg once weekly, 40 mg CAPSULE SUMMARY Infliximab is a chimeric every other week, or antibody composed of both placebo) of 154 patients Numerous reports suggest that biologic human and mouse proteins with moderate to severe therapies are effective for patients with targeting TNFa. Infliximab disease, 17.6% of patients moderate to severe hidradenitis binds to both soluble and dosed weekly, 9.6% of suppurativa transmembrane TNFa,2 patients dosed every other The strongest evidence supports the use which may explain its more week, and 3.9% of placebo of adalimumab and infliximab. encouraging results relative patients achieved clinical to etanercept in the treatment response at week 16. Other biologics might also offer benefit of HS. Investigators postulated a in the treatment of hidradenitis Ten cohort studies, with at possible dose-dependent suppurativa, but more data are required least 4 and no more than 11 relationship with respect to to determine which agents will have a patients in each study, have serious adverse event rates role. been published regarding (7.8%, 5.8%, and 3.9%, the use of infliximab in parespectively). Injection site tients with HS. The majority of treated patients had reactions were common in both adalimumabmoderate to severe disease (Hurley stage II or III), treated patients and those receiving vehicle (20% with most treatments consisting of infusions of and 14%, respectively). Headache was a frequently 5 mg/kg of infliximab at weeks 0, 2, and 6. reported adverse event.11 Outcome measures were often subjective and not validated. Nearly all studies found that some of the Ustekinumab patients improved with treatment. Ustekinumab, a human, anti-p40 monoclonal Grant et al9 performed the only randomized, antibody, is a biologic used in the treatment of placebo-controlled trial on the use of infliximab in patients with psoriasis. P40 is a shared subunit of the treatment of HS. Investigators enrolled 38 pahuman interleukins (ILs) -12 and -23. IL-12 activates tients and found that 26% of patients in the treatment T cells, which will secrete the classic TH1 cytokines arm experienced a $50% decrease in disease interferon-g and TNFa. IL-23 promotes the survival severity compared to 5% of patients in the placebo of TH17 cells, production of IL-17A and neutrophil group. In addition, DLQI, pain, and Physician Global recruitment, and downstream TNFa expression. Assessments all significantly improved from baseline A study of 3 patients and 3 case reports highin the treatment arm but not in the placebo arm. lighted treatment with ustekinumab and found that the medication was well-tolerated and produced a partial to complete response in 5 patients, with Adalimumab follow-up exceeding 6 months.12-15 Of note, the Adalimumab is a fully humanized monoclonal onset of action was not rapid, with improvement antibody that corresponds to the human immunodescribed as taking several months before becoming globulin G1 and has heavy and light chain variable apparent.16,17 No significant adverse reactions have regions exhibiting specificity for human TNFa. It been reported, but only a handful of patients with HS binds with high affinity to both soluble and have been treated with ustekinumab. membrane- bound TNFa.2 Retrospective analysis of case reports and case series point to significant efficacy of adalimumab in Anakinra treating HS. Moreover, it is the most well-studied Anakinra is a recombinant IL-1-alfa (IL-1a) biologic with multiple, larger-sized, randomized, receptor antagonist that competitively binds to IL-1 controlled studies conducted. In a prospective, receptors and prevents IL-1 accessory protein from randomized, double-blind, placebo-controlled study interacting with the receptor, resulting in signal of adalimumab treatment (a subcutaneous dose of blockade. Both the activity of IL-1a and IL-1b are d

d

d

Drug, author(s), and year

Etanercept Cusack and Buckley, 20063

No. of patients

6

Hurley stage

Regimen

II and III 25 mg SC, BIW

Giamarellos-Bourboulis et al, 20084

10

NR

50 mg SC, wkly

Lee et al, 20096

15

NR

50 mg SC, wkly

Sotiriou et al, 20095

4

Adams et al, 20107

20

NR

50 mg SC, BIW

Infliximab Sullivan et al, 200337

5

NR

5 mg/kg IVIN, q month 3 1-2

Fardet et al, 200738

7

Fernandez-Vozmediano and Armario-Hita, 200739 Usmani et al, 200740

6

Mekkes and Bos, 200841

4 11

Delage et al, 201143

7

Lesage et al, 201244

10

Paradela et al, 201245

10

Grant et al, 20109

38

Physician assessment: 2 patients improved moderately and 3 markedly NR 5 mg/kg IVIN, at weeks 0, 2, 6, Physician assessment: 2 patients and 10 markedly improved, 2 had minor improvement III 5-10 mg/kg at wks 0, 2 and 6, PGA: 4 patients markedly improved, then every 4 wks 2 moderately improved NR 5 mg/kg IVIN, at 0, 2, 6 weeks 2 ‘‘good responses,’’ 1 ‘‘mild,’’ and 1 ‘‘poor’’ NR 5 mg/kg IVIN, at 0, 2, and 6 wks Mean skin scores significantly reduced from 165 to 89 NR 5 mg/kg IVN at wks 0, 2, and 6, 70% mean improvement in Sartorius then q 8 weeks scale at wk 14 II and III 5 mg/kg IVIN, at wks 0, 2, and 6, 70% global improvement then q 8 wks II and III 5 mg/kg IVIN at wks 0, 2, and 6, DLQI decreased from mean of 20 to 6 then q 4 wks II and III 5 mg/kg IVIN at wks 0, 2, and 6, ‘‘Response’’ observed in 8 patients, then q 8 wks no ‘‘response’’ in 2 patients; ‘‘relapse’’ occurred in 4 patients NR 5 mg/kg IVIN at wks 0, 2, and 6 26% of infliximab patients had a [50% reduction in HSSI vs. 5% in the placebo group

Study type

24 wks

Prospective cohort

24 wks

Prospective cohort

12 wks

Prospective cohort

6 mos

Prospective cohort

12 wks (RCT phase), RCT 24 wks openlabel phase 3 wks-6 mos

Retrospective cohort

10 wks

Prospective cohort

NR

Retrospective cohort

NR

Retrospective cohort

12 mos

Prospective cohort

2-4 mos

Retrospective cohort

Mean 72 wks

Retrospective cohort

12 mos

Prospective cohort

49 wks

Prospective cohort

8 wks

RCT

NOVEMBER 2015

4

61% reduction in disease activity; 64% improvement in DLQI VAS scores decreased significantly below baseline in 6/10 patients at 24 wks 3/15 patients experienced 50% reduction of Physical Global Scores Mean self- reported improvement 68.8%; DLQI improved 66.5% No significant difference in physician, patient, or DLQI scores

Study duration

J AM ACAD DERMATOL

Lasocki et al, 201042

II and III 25 mg SC, BIW and 50 mg BIW

Outcomes

S84 Lee and Eisen

Table I. Study data summary

Kimball et al, 201211

154

Ustekinumab Gulliver et al, 201112 Sharon et al, 201213

3 1

Baerveldt et al, 201314

1

Santos-Perez et al, 201415

1

Anakinra van der Zee and Prens, 201346 Zarchi et al, 201320 Menis et al, 201447 Leslie et al, 201448

II and III 80 mg SC at wks 0 then 40 mg SC q2 wks 2-3 40 mg SC wkly and 40 mg SC every other wk

Significant improvement at wk 2 but 3 mos not at wk 12 About 17.6% of patients on weekly 3 mos dosing and 9.6% on every other weekly dosing showed significant improvement

RCT

II and III 45 mg SC at wks II 45 mg SC at wks then increased q8 wks II 45 mg SC at wks then q12 wks II and III 45 mg SC at wks then q12 wks

0, 4, and 16 0, 4, and 12, to 90 mg SC

1 patient reported [50% response rate Partial response

6 mos At least 28 wks

Retrospective cohort Case report

0, 4, and 12,

Complete remission

36 mos

Case report

0, 4, and 12,

Complete remission

1.5 yrs

Case report

RCT

1

III

100 mg SC daily

Worsening of HS

5 mos

Case report

1 2

III III

200 mg SC daily 100 mg SC daily

Significant improvement in DLQI No improvement to worsening on PGA and DLQI Improvement of VAS, DLQI and Sartorius

1 yr 8-12 wks

Case report Case report

8 wks

Prospective cohort

6

II and III 100 mg SC daily

J AM ACAD DERMATOL

21

VOLUME 73, NUMBER 5

Adalimumab Miller et al, 201110

BIW, Twice weekly; DLQI, Dermatology Life Quality Index; HS, hidradenitis suppurativa; HSSI, hidradenitis suppurativa severity index; IVIN, intravenous infusion; NR, not reported; PGA, Physician’s Global Assessment; RCT, randomized controlled trial; SC, subcutaneous injection; VAS, visual analog scale.

Lee and Eisen S85

J AM ACAD DERMATOL

S86 Lee and Eisen

affected. This, in turn, results in reduced T cell proliferation, prostaglandin E2 secretion, metalloproteinase secretion, hyaluronic acid secretion, and proteoglycan degradation.18 IL-1 cytokine elevation has been demonstrated in HS. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome19 is believed to be related to autoimmune syndromes associated with sterile abscesses and with IL-1a signaling. Targeting the IL-1 pathway has been successful in pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome19 and other autoinflammatory entities, such as rheumatoid arthritis. A total of 10 patients have been reported to be treated with anakinra, with 7 showing a response to anakinra on daily subcutaneous doses ranging from 100 to 200 mg. Injection site reactions were common but tended to decrease with treatment. One patient described multiple episodes of Staphylococcus aureus bacteria folliculitis.20 A review of patients with rheumatoid arthritis found a higher rate of infection (1.8% in the treatment group vs. 0.6% in the control group).18

SAFETY OF BIOLOGICS Many adverse events have been reported in association with the use of biologics.21-29 The greatest concerns involve the risk of infection, especially the reactivation of latent tuberculosis,30 demyelinating disorders,31 and the possibility of cancer resulting from long-term immunosuppression. Given that no data have emerged to suggest that patients with HS are at an elevated risk for developing complications caused by biologic therapy relative to patients with other inflammatory conditions, the side effect profile of biologics in patients with psoriasis or rheumatoid arthritis can be extrapolated to the HS setting. A recent multiinstitution, longitudinal study with 466 psoriasis patients and 22,311 patient years of observation calculated the cumulative incidence rate for serious infections at 1.45 per 100 patient years (n = 323) across treatment cohorts, and rates of 0.83, 1.47, 1.97, and 2.49 per 100 patient years for ustekinumab, etanercept, adalimumab, and infliximab, respectively. This compared with 1.05 and 1.28 per for patients treated with nonbiologic/ nonmethotrexate and nonbiologic/methotrexate medications.32 A meta-analysis of 74 randomized, placebocontrolled trials involving biologic treatments calculated 0.84% of patients in the treatment arms developed cancers versus 0.64% of control subjects,31 indicating a relatively small, short-term risk of malignancy for patients who were taking

NOVEMBER 2015

biologics. Additional study is required to assess the long-term risks of malignancy.

DATA ANALYSIS Estimates of treatment effects for patients with HS managed with biologics vary widely. These heterogeneous results likely reflect the relatively small datasets and poor quality of many studies currently in the literature. Variations in response to therapy may be in part explained by underlying genetic differences in treated individuals, as found by Savva et al.33 Despite limitations of most studies determining the efficacy of biologics in the management of HS, randomized trials do suggest that both infliximab and adalimumab significantly reduce HS disease severity. This is a standard that no other HS treatment, except laser therapy, meets.34-36 Looking at safety, experience with biologics for the treatment of other inflammatory disorders now spans more than a decade, and the safety of these agents appears acceptable. Accordingly, in patients with HS who are refractory to other treatment options, biologic therapy with infliximab or adalimumab appears to be a reasonable option. More data are necessary before any recommendations regarding the use of other biologics can be made, such as anakinra, etanercept, and ustekinumab. In conclusion, as we deepen our understanding of the inflammatory pathways that characterize HS, we can aim to optimize the use of biologic medications, thereby reducing the burden of disease for patients with HS. Both adalimumab and infliximab boast the most robust evidence to support their use. While other biologic agents show promise, the scarcity of high-quality data fails to provide sufficient evidence for their efficacy at the current time. REFERENCES 1. Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29:619-644. 2. Scallon B, Cai A, Solowski N, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther. 2002;301:418-426. 3. Cusack C, Buckley C. Etanercept: effective in the management of hidradenitis suppurativa. Br J Dermatol. 2006;154:726-729. 4. Giamarellos-Bourboulis EJ, Pelekanou E, Antonopoulou A, et al. An open-label phase II study of the safety and efficacy of etanercept for the therapy of hidradenitis suppurativa. Br J Dermatol. 2008;158:567-572. 5. Sotiriou E, Apalla Z, Ioannidos D. Etanercept for the treatment of hidradenitis suppurativa. Acta Derm Venereol. 2009;89: 82-83. 6. Lee RA, Dommasch E, Treat J, et al. A prospective clinical trial of open-label etanercept for the treatment of hidradenitis suppurativa. J Am Acad Dermatol. 2009;60:565-573.

J AM ACAD DERMATOL VOLUME 73, NUMBER 5

7. Adams DR, Yankura JA, Fogelberg AC, Anderson BE. Treatment of hidradenitis suppurativa with etanercept injection. Arch Dermatol. 2010;146:501-504. 8. Gisondi P, Girolomoni G. Impact of TNF-alpha antagonists on the quality of life in selected skin diseases. G Ital Dermatol Venereol. 2013;148:243-248. 9. Grant A, Gonzalez T, Montgomery MO, Cardenas V, Kerdel FA. Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. J Am Acad Dermatol. 2010; 62:205-217. 10. Miller I, Lynggaard CD, Lophaven S, Zachariae C, Dufour DN, Jemec GBE. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa. Br J Dermatol. 2011;165:391-398. 11. 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;157:846-855. 12. Gulliver WP, Jemec GB, Baker KA. Experience with ustekinumab for the treatment of moderate to severe hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2012; 26:911-914. 13. Sharon VR, Garcia MS, Bagheri S, et al. Management of recalcitrant hidradenitis suppurativa with ustekinumab. Acta Derm Venereol. 2012;92:320-321. 14. Baerveldt EM, Kappen JH, Thio HB, et al. Successful long-term triple disease control by ustekinumab in a patient with Behc¸et’s disease, psoriasis and hidradenitis suppurativa. Ann Rheum Dis. 2013;72:626-627. 15. Santos-P erez MI, Garcıa-Rodicio S, Del Olmo-Revuelto MA, Pozo-Roman T. Ustekinumab for hidradenitis suppurativa: a case report. Actas Dermosifiliogr. 2014;105:720-722. 16. Neovius M, Sundstrom A, Simard J, et al. Small-area variations in sales of TNF inhibitors in Sweden between 2000 and 2009. Scand J Rheumatol. 2011;40:8-15. 17. Martin-Ezquerra G, Masferrer E, Masferrer-Niubo M, et al. Use of biological treatments in patients with hidradenitis suppurativa. J Eur Acad Dermatol Venereol. 2015;29:56-60. 18. Mertens M, Singh JA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol. 2009;36:1118-1125. 19. Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)—a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol. 2012;66:409-415. 20. Zarchi K, Dufour DN, Jemec GBE. Successful treatment of severe hidradenitis suppurativa with anakinra. JAMA Dermatol. 2013;149:1192-1194. 21. Maalouf E, Faye O, Poli F, Cosnes A, Revuz J. Fatal epidermoid carcinoma in hidradenitis suppurativa following treatment with infliximab. Ann Dermatol Venereol. 2006;133(5 pt 1): 473-474. 22. Benitez-Macias JF, Garcia-Gil D, Brun-Romero FM. Fatal pneumococcal sepsis in patient with hidradenitis suppurative treated with infliximab. Med Clin (Barc). 2008;131:799. 23. van Rappard DC, Mooij JE, Baeten DL, Mekkes JR. New-onset polyarthritis during successful treatment of hidradenitis suppurativa with infliximab. Br J Dermatol. 2011;165:194-198. 24. Rowe BW, Gala-Lopez B, Tomlinson C, Girgis S, Shapiro JA. Fulminant hepatic failure necessitating transplantation following the initiation of infliximab therapy: a cautionary tale times two. Transpl Int. 2013;26:e110-e112. 25. Scheinfeld N. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma. Dermatol Online J. 2014;20:3.

Lee and Eisen S87

26. Acquacalda E, Roux CH, Albert C, et al. New onset of articular inflammatory manifestations in patients with hidradenitis suppurativa under treatment with infliximab. Joint Bone Spine. March 13, 2015. http://dx.doi.org/10.1016/j.jbspin.2015.01.020 [Epub ahead of print]. 27. Arriola-Villalobos P, Diaz-Valle D, Alejandre-Alba N, et al. Bilateral Candida chorioretinitis following etanercept treatment for hidradenitis suppurativa. Eye (Lond). 2008;22:599-600. 28. Pellegrino M, Taddeucci P, Peccianti C, Mei S, Fioravanti A, Fimiani M. Etanercept induced hidradenitis suppurativa. G Ital Dermatol Venereol. 2011;146:503-504. 29. Ferrer-Marin F, Amigo ML, Vicente V. Leukaemic transformation in patients with haematological disease receiving tumour necrosis factor inhibitors. Clin Drug Investig. 2012;32:423-426. 30. Rubbert-Roth A. Assessing the safety of biologic agents in patients with rheumatoid arthritis. Rheumatology (Oxford). 2012;51(suppl 5):v38-v47. 31. Askling J, Fahrbach K, Nordstrom B, et al. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf. 2011;20:119-130. 32. Kalb RE, Fiorentino DF, Lebwohl MG, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. May 13, 2015. http: //dx.doi.org/10.1001/jamadermatol.2015.0718 [Epub ahead of print]. 33. Savva A, Kanni T, Damoraki G, et al. Impact of Toll-like receptor-4 and tumour necrosis factor gene polymorphisms in patients with hidradenitis suppurativa. Br J Dermatol. 2013; 168:311-317. 34. Tierney E, Mahmoud BH, Hexsel C, Ozog D, Hamzavi I. Randomized control trial for the treatment of hidradenitis suppurativa with a neodymium-doped yttrium aluminium garnet laser. Dermatol Surg. 2009;35:1188-1198. 35. Xu LY, Wright DR, Mahmoud BH, Ozog DM, Mehregan DA, Hamzavi IH. Histopathologic study of hidradenitis suppurativa following long-pulsed 1064-nm Nd:YAG laser treatment. Arch Dermatol. 2011;147:21-28. 36. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol. 2009;60:539-561. 37. Sullivan TP, Welsh E, Kerdel FA, Burdick AE, Kirsner RS. Infliximab for hidradenitis suppurativa. Br J Dermatol. 2003; 149:1046-1049. 38. Fardet L, Dupuy A, Kerob D, et al. Infliximab for severe hidradenitis suppurativa: transient clinical efficacy in 7 consecutive patients. J Am Acad Dermatol. 2007;56:624-628. 39. Fernandez-Vozmediano JM, Armario-Hita JC. Infliximab for the treatment of hidradenitis suppurativa. Dermatology. 2007;215: 41-44. 40. Usmani N, Clayton TH, Everett S, Goodfield MD. Variable response of hidradenitis suppurativa to infliximab in four patients. Clin Exp Dermatol. 2007;32:204-205. 41. Mekkes JR, Bos JD. Long-term efficacy of a single course of infliximab in hidradenitis suppurativa. Br J Dermatol. 2008;158: 370-374. 42. Lasocki A, Sinclair R, Foley P, Saunders H. Hidradenitis suppurativa responding to treatment with infliximab. Australas J Dermatol. 2010;51:186-190. 43. Delage M, Samimi M, Atlan M, et al. Efficacy of infliximab for hidradenitis suppurativa: assessment of clinical and biological inflammatory markers. Acta Derm Venereol. 2011;91:169-171. 44. Lesage C, Adnot-Desanlis L, Perceau G, et al. Efficacy and tolerance of prolonged infliximab treatment of

S88 Lee and Eisen

moderate-to-severe forms of hidradenitis suppurativa. Eur J Dermatol. 2012;22:640-644. 45. Paradela S, Rodriguez-Lojo R, Fernandez-Torres R, Arevalo P, Fonseca E. Long-term efficacy of infliximab in hidradenitis suppurativa. J Dermatolog Treat. 2012;23:278-283. 46. van der Zee HH, Prens EP. Failure of anti-interleukin-1 therapy in severe hidradenitis suppurativa: a case report. Dermatology. 2013;226:97-100.

J AM ACAD DERMATOL

NOVEMBER 2015

47. Menis D, Maronas-Jimenez L, Delgado-Marquez AM, Postigo-Llorente C, Vanaclocha-Sebastian F. Two cases of severe hidradenitis suppurativa with failure of anakinra therapy. Br J Dermatol. 2015;172:810-811. 48. Leslie KS, Tripathi SV, Nguyen TV, Pauli M, Rosenblum MD. An open-label study of anakinra for the treatment ofmoderate to severe hidradenitis suppurativa. J Am Acad Dermatol. 2014;70: 243-251.