Systematic review of immunomodulatory therapies for hidradenitis suppurativa

Figures & data

Table 1 Hurley staging of HS

Stage I (mild)	Abscess formation, single or multiple, without sinus tracts and cauterization.
Stage II (moderate)	Recurrent abscesses with tract formation and cicatrization, single or multiple, widely separated lesions.
Stage III (severe)	Diffuse or near-diffuse involvement, or multiple interconnected tracts and abscesses across the entire area.

Note: Data from Hurley.⁸

Abbreviation: HS, hidradenitis suppurativa.

Table 2 Scoring systems used in grading HS severity

HiSCR^Citation99	≥50% reduction in inflammatory lesion count (abscesses and inflammatory nodules) AND No increase in abscesses or draining fistulas compared to baseline
HS-PGA^Citation11	Clear	No inflammatory or non-inflammatory nodules
	Minimal	Only the presence of non-inflammatory nodules
	Mild	1–4 inflammatory nodules OR 1 abscess or draining fistula AND no inflammatory nodules
	Moderate	≥5 inflammatory nodules OR 1 abscess or draining fistula AND ≥1 inflammatory nodules OR 2–5 abscesses or draining fistulas AND <10 inflammatory nodules
	Severe	2–5 abscesses or draining fistulas AND ≥10 inflammatory nodules
	Very Severe	>5 abscesses or draining fistulas
mSS^Citation100	A	Number of regions affected (3 points per region): Right axilla Left axilla Right groin Left groin Right gluteal region Left gluteal region Other region
	B	For each…: Nodule: 1 point Fistula: 6 points
	C	For each affected region, longest distance between two relevant lesions: <5 cm: 1 point 5–10 cm: 3 points >10 cm: 9 points
	D	For each affected region: If lesions not clearly separated by normal skin: 9 points
	The mSS is the total of the subtotals of A to D.
HSSI^Citation101	Points scored	No. of sites	BSA affected (%)	No. of lesions (erythematous, painful)	Drainage (dressing changes per working or leisure hour)	Pain (VAS)
	0	0	0	0	0	0–1
	1	1	1	1
	2	2	2–3	2–3	1	2–4
	3	3	4–5	4–5	>1	5–7
	4	≥4	>5	>5		8–10
	Sites: Left armpit, right armpit, left side of chest, right side of chest, left groin, right groin, perianal area, sacral area and perineal area. The HSSI is the total of all five assessed domains, with a minimum score of 0 and a maximum score of 19.
IHS4^Citation102	A	Number of nodules
	B	Number of abscesses
	C	Number of draining tunnels
	The IHS4 is derived by the formula: A x 1+ B x 2+ C x 4

Abbreviations: HiSCR, hidradenitis suppurativa clinical response; HS-PGA, HS physician’s global assessment; mSS, modified sartorius score; HSSI, HS severity index; BSA, body surface area; IHS4, International HS Score System.

Figure 1 Selection of articles identified by PubMed search.

Figure 2 Selection of articles identified by Clinicaltrials.gov search.

Table 3 Biologics and other immunomodulatory therapies reported in the treatment of HS

TNF-α inhibitors	Adalimumab*^Citation10,Citation12,Citation14^–^Citation16,Citation23^–^Citation27 Infliximab^Citation9,Citation31,Citation32 Etanercept^Citation51 Golimumab^Citation53,Citation54 Certolizumab^Citation56
IL-1 inhibitors	Anakinra^Citation58,Citation60,Citation103 Canakinumab^Citation62,Citation63 Bermekimab^Citation66 MEDI8968^Citation70
IL-12/-23 inhibitors	Ustekinumab^Citation72
IL-17 inhibitors	Secukinumab^Citation74^–^Citation76 CJM112^Citation79 Bimekizumab^Citation82
IL-23 inhibitors	Guselkumab^Citation84^–^Citation86
Selective PDE-4 inhibitors	Apremilast^Citation89,Citation90,Citation104
Complement C5a inhibitors	IFX-1^Citation91^–^Citation93
CD-11a inhibitors	Efalizumab**^Citation105
CD-20 inhibitors	Rituximab^Citation95
JAK-1 inhibitors	INCB054707^Citation96,Citation97

Notes: ^aFDA-approved for treatment of HS

^bNo longer available, and thus excluded from further review.

Abbreviation: HS, hidradenitis suppurativa.

Table 4 Articles included in systematic review

Case reports, case series and retrospective studies
Case reports
Study	Subject characteristics	Therapies	Dose	Treatment duration	Efficacy	Complications
Koilakou S et al^Citation106	One 38-year-old male	ADA	40 mg EOW	NR	No	None
Benhadou F et al 2018^Citation22	One 55-year-old female	ADA	160 mg once	1 week	Yes	Erythroderma
Van der Zee HH et al 2013^Citation53	One 51-year-old female	ADA, GOL, ANK	ADA 40 mg EOW, GOL 50 mg monthly, ANK 100 mg monthly	ADA for 2 years, GOL for 1 year, ANK for 1 year	All ineffective	None
Moul DK et al 2006^Citation107	One 67-year-old male	ADA	40 mg EOW	5 months	Yes	None
Harde V et al 2008^Citation108	One 32-year-old male	ADA	80 mg once, then 40 mg weekly	6 months	Yes	None
de Wet J et al 2017^Citation17	One 42-year-old male	ADA	160 mg at week 0, 80 mg at week 2, and 40 mg weekly for 5 weeks	8 weeks	Yes	None
Samycia M et al^Citation109	One 48-year-old male	ETA, INF, ADA	ETA 50 mg weekly, then twice weekly, INF 5 mg/kg, then 10 mg/kg every 6 weeks, ADA 80 mg at week 0 then 40 mg EOW then weekly	ETA for 4 months, INF for 1 year 6 months, ADA for 1 year	No Yes, for 1 year Yes	Fatigue (from INF)
Diamantova et al 2014^Citation110	One 50-year-old female	ADA	80 mg at week 0 then 40 mg EOW	8 weeks	Yes	None
Bosnić et al 2016^Citation111	One 39-year-old male	ADA	40 mg EOW	1 year	Yes	None
Saraceno et al 2015^Citation18	One 50-year-old male	ADA	40 mg EOW	36 weeks	Yes	None
Bessaleli et al 2018^Citation112	One 33-year-old female	ADA	40 mg, then increased to 80 mg weekly	8 months	Yes	Cervical squamous cell carcinoma in situ
Crowley EL et al 2018^Citation113	One 32-year-old male	ADA	80 mg at week 0 and then 40 mg weekly	3 years	Yes	Oral candidiasis
Molina-Leyva et al 2018^Citation114	One 39-year-old female	ADA	NR	16 weeks	DLQI reduced from 18 to 0 at week 4 and 16	None
Gorovoy et al 2009^Citation115	One 47-year-old female	INF, ADA	INF NR, ADA 40 mg EOW	15 months for each biologic	Initial response for INF, good response for ADA	Infusion reaction with urticaria (INF)
Murphy et al 2015^Citation19	One 26-year-old female	INF, ADA	INF 5 mg/kg for 2 doses, ADA 160 mg/80 mg then 40 mg EOW	INF NR, ADA for 2 months	Response to both	Drug hypersensitivity (INF)
Friedman et al 2018^Citation13	One 48-year-old female	ANK	100 mg/day for 9 months, then 200 mg/day for 15 months	24 months	Moderate response	Drug-induced sarcoidosis
Zarchi et al 2013^Citation116	One 37-year-old female	ANK	200 mg/day	1 year	Yes	Staphylococcus aureus pustular folliculitis
Jaeger T et al 2013^Citation64	One 27-year-old male	CAN	150 mg every 3–6 weeks for 8 injections	NR	Yes	NR
Tekin B et al 2017^Citation65	One 27-year-old male	INF, CAN	INF 5 mg/kg for 8 sessions, CAN 150 mg every 4 weeks for 3 doses	NR	Slight improvement with INF, worsening with CAN	Worsening of HS with CAN
Zangrilli A et al 2008^Citation117	One 32-year-old male	ETA	50 mg 2x/week for 24 weeks, then 25 mg 2x/week for 24 weeks	48 weeks	Yes	None
Tursi A 2016^Citation54	One 42-year-old female	GOL	200 mg once then 100 mg every 4 weeks	NR	Yes	None
Roussomoustakaki M et al 2003^Citation38	One 29-year-old female	INF	5 mg/kg at 0, 2 and 6 weeks	6 weeks	Yes	None
Adams DR et al 2003^Citation118	One 17-year-old male	INF	5 mg/kg at 0, 2, 6 weeks, and 7 months	7 months	Yes	None
Rosi YL et al 2005^Citation119	One 30-year-old female	INF	5 mg/kg at 0, 2 and 6 weeks	6 weeks	Yes	None
Husein-ElAhmed H et al 2011^Citation120	One 47-year-old male	INF	4.6 mg/kg at weeks 0, 2, 6, 10	10 weeks	Yes, but recurrence in 2 weeks	None
von Preussen AC et al 2012^Citation121	One 42-year-old female	INF	5 mg/kg at 0, 2 and 6 weeks and then every 8 weeks	NR	Yes	None
Montes-Romero JA et al 2008^Citation37	One 39-year-old male	INF	5 mg/kg at weeks 0, 2, 6 and 14	NR	Yes	None
Goertz RS et al 2008^Citation41	One 54-year-old male	INF	5 mg/kg for 7 infusions	2 years	Yes, but effect plateaued	New superinfection
Blazquez I et al 2013^Citation39	One 50-year-old female	INF	INF 5 mg/kg at 0, 2 and 6 weeks and then every 8 weeks	6 months	Yes	None
Groleau PF et al 2015^Citation40	One 51-year-old male	INF	I5 mg/kg at 0, 2 and 6 weeks and then 7.5 mg/kg every 8 weeks for 1 year, then 5 mg/kg every 8 weeks twice, then 2.5 mg/kg every 8 weeks twice Stopped for 7 months, then 5 mg/kg every 8 weeks when relapsed	NR	Yes, relapsed after cessation	None
Martínez F et al 2001^Citation42	One 30-year-old male	INF	5 mg/kg for 2 doses	NR	Yes	Generalized erythema and dyspnea
Lebwohl B et al 2003^Citation122	One 21-year-old male	INF	NR	NR	Yes, but recurred on prolonged sitting	None
Thielen AM et al 2006^Citation123	One 48-year-old male	INF	5 mg/kg at 0, 2 and 6 weeks then every 8 weeks	104 weeks	Yes	Limited herpes zoster
Gori A et al 2012^Citation44	One 19-year-old male	INF	5 mg/kg at 0, 2 and 6 weeks then every 8 weeks	14 weeks	Yes	Acne
Alecsandru D et al 2010^Citation124	One 47-year-old male	INF	5 mg/kg at 0, 2 and 6 weeks then every 8 weeks	NR	Yes, flared upon stopping	None
Poulin Y et al 2009^Citation125	One 25-year-old female	ETA, INF	ETA 50 mg twice a week, INF 5 mg/kg at 0, 2 and 6 weeks then every 6 weeks	26 months of ETA, 20 months of INF	Worsened with ETA, improved with INF	ETA caused flare of HS
Staub J et al 2015^Citation36	One 22-year-old female	ETA, ADA, ANK, INF	ETA, ADA and ANK NR, INF 5 mg/kg at 0 and 2 weeks then every 8 weeks	10 months of ETA, 5 months of ADA, 20 months of INF Not stated for ANK	Improved with INF in combination with dapsone, steroids and cyclosporine but relapsed on tailing cyclosporine	None
Ozer I et al 2016^Citation35	One 43-year-old male	INF	5 mg/kg at 0, 2 and 6 weeks then every 8 weeks	2 years	Yes	None
Kozub P et al 2012^Citation126	One 53-year-old female	INF	500 mg at 0, 2 and 6 weeks then every 8 weeks	43 weeks	Initial improvement but plateaued until addition of dapsone	None
Vossen MG et al 2011^Citation43	One 21-year-old male	ETA, INF	ETA 50 mg/week, INF 5 mg/kg	NR	NR	Gemella morbillorum bacteremia
Takahashi H et al 2017^Citation95	One 19-year-old male	RIT	200 mg for 2 doses 1 year apart	1 year	Yes	None
Thorlacius L et al 2017^Citation74	One 47-year-old male	ADA, INF, ANK, SEC	ADA, INF, ANK NR, SEC 300 mg/week for 4 weeks then every 4 weeks after	7 years	Not improved with ADA, INF, ANK. Responded to SEC	Oral candidiasis (SEC)
Schuch A et al 2017^Citation75	One 24-year-old male	ADA, INF SEC	ADA, INF NR, SEC 300 mg/week for 4 weeks then every 4 weeks after	NR	Not improved with ADA and INF, responded to SEC	None
Giuseppe P et al 2018^Citation127	One 37-year-old male	INF, SEC	INF 5 mg/kg, SEC 300 mg/week for 4 weeks then every 4 weeks after	NR	Partial improvement with INF, improved with SEC	None
Jørgensen AR et al 2018^Citation128	One 36-year-old female	INF, ADA, UST, SEC	INF, ADA, UST NR, SEC 300 mg/week for 5 weeks then every month	1 year	No response to INF, ADA, UST, improved with SEC but small relapse	Throat infections, fever
Santos-Pérez MI et al 2014^Citation129	One 50-year-old female	ADA, UST	ADA 80 mg, then 40 mg every 2 weeks, UST 45 mg at weeks 0, 4 and then every 12 weeks	2 years of ADA, 1.5 years of UST	Stable then worsened on ADA, improved with UST but 2 exacerbations reported	None
Sharon VR et al 2012^Citation130	One 55-year-old male	ADA, UST	ADA NR, UST 45 mg at weeks 0, 4 and 12, then 90 mg every 8 weeks	NR	Did not respond to ADA, improved with UST but flares 2 weeks prior to next dose	None
Scheinfeld N 2014^Citation45	One 47-year-old male	INF	500 mg for 3 courses	NR	NR	Metastatic cutaneous squamous cell carcinoma
Case series
Study	Subject characteristics	Therapies	Dose	Treatment duration	Efficacy	Complications
Blanco R et al 2009^Citation131	Six patients, two males and four females	ADA in six, ETA in one	ADA 40 mg EOW, increased to weekly if inadequately controlled, decreased to 3-weekly if in remission	Mean of 21.5 months	ETA ineffective, ADA effective	Pain at injection site, severe facial cellulitis in one patient
Chinniah N et al 2014^Citation132	Six patients, four males and two females	ADA in three cases, INF in four cases, ETA in one case**	NR	Mean 25.3 months	Significant response to ADA in two, INF in three, ETA in one	Neurological adverse events in one patient on ADA
Houriet C et al 2017^Citation63	Two (One male, one female)	CAN	One given 150 mg monthly, one given 150 mg on day 1 and 15 and then monthly	One for 26 months, one for 12 months	Reduction in Sartorius score and VAS for both patients	None
Sun NZ et al 2017^Citation62	Two females	CAN and ANK in one, ADA, INF and CAN in one	INF 5 mg/kg at week 0, 2 and 6, CAN 150 mg every 8 weeks, ANK 100 mg daily for first patient, ADA 40 mg weekly, INF 6 mg/kg and CAN 150 mg weekly for second patient	NR	INF effective in one patient, ADA partial response in same patient	INF - hypersensitivity reaction in first patient, suspicion of drug-related interstitial nephritis in second patient
Sand FL et al 2015^Citation56	29 patients	ADA in 22, ETA in five, INF in six, CER in two**	ADA 40 mg once weekly, ETA 50 mg once weekly, INF 5 mg/kg every 8 weeks, ADA 40 mg once weekly	Mean of 13 months (1–50 months)	12 out of 22 responded to ADA, two of five to ETA, one of six to INF, none of two for CER	ADA – Meningealia, headache, fever in one patient, pneumonia in two patients, visual disturbances and headache in one patient; ETA – urosepticemia in one patient, sebopsoriasis in one patient; INF –sensory and motor polyneuropathy, myalgia and arthralgia in one patient, recurrent tonsillitis in one patient
Zhao CY et al 2018^Citation21	Four males	ADA	NR	10–60 months	50–100% improvement	One with development of melanoma in situ, one with worsening of Charcot-Marie-Tooth syndrome, one with drug-induced lupus
Patil 2018^Citation133	Two males	ADA biosimilar (ZRC-3197)	40 mg weekly for 3 weeks, then EOW for 3 months	3 months and 3 weeks	>50% reduction in abscess and inflammatory nodule count in both patients	None
Menis et al 2014^Citation103	Two males	ANK	100 mg daily	12 weeks	No	One with worsening of HS
Cusack et al 2006^Citation134	Six females	ETA	25 mg twice weekly	17–40 weeks	All six improved, between 44% and 73% in DLQI reduction	Increased frequency of upper respiratory tract infections in one patient
Lasocki et al 2010^Citation135	Four (One male, three female)	INF	5 mg/kg at week 0, 2 and 6, then 8-weekly maintenance infusions.	38–54 weeks	Improvement in all patients, but with recurrence in all after cessation of therapy	Headache and vomiting in one patient
Lozeron et al 2009^Citation20	One male	INF	5 mg/kg at 0, 2, 6, 12 and 18 weeks	18 weeks	Not effective	Lewis-Summer Syndrome (demyelinating neuropathy)
Elkjaer et al 2008^Citation136	Two males	INF	5 mg/kg/day at 0, 2 and 6 weeks and then 5 weekly	NR	Effective	Infusion reactions in one patient
Antonucci et al 2008^Citation137	Two (one male, one female)	INF	5 mg/kg on weeks 0, 2 and 6 and then every 8 weeks	59 weeks	Effective in one, ineffective in one	None
Delage et al 2011^Citation32	Seven (Three males, Four females)	INF	5 mg/kg on weeks 0, 2 and 6 and then every 8 weeks	6–110 weeks	Effective in six	One with eczema-like eruption, one with pretragian abscess
Brunasso et al 2008^Citation138	Seven (Three males, four females)	INF	5 mg/kg on weeks 0, 2 and 6 and then every 8 weeks	Mean 58.6 weeks (4–72)	Improvements in pain, discharge, area reduction and DLQI. 3 with new lesions during therapy	One with adverse drug reaction, not further specified
Moschella 2007^Citation139	Three (One male, two females)	INF	5 mg/kg on weeks 0, 2 and 6 and then varying subsequent dosing	54–80 weeks	Effective in all	None
Sullivan et al 2003^Citation140	Five (One male, four females)	INF	5 mg/kg at week 0 for all five patients, and again at week 4–6 for three patients	0– 6 weeks	Effective in all	Presumed Mycobacterium tuberculosis lymph node infection in one patient
Torres et al 2010^Citation141	Two patients	INF	5 mg/kg on weeks 0, 2 and 6 and then every 8 weeks	7 months	Ineffective	None
Usmani et al 2006^Citation142	Four patients (two males, two females)	INF	5 mg/kg, varying dosing	Up to 11 months	Two with good response, one with mild response, one with poor response	One with INF-induced lupus, one with infusion reaction
Fernández-Vozmediano et al 2007^Citation143	Six patients (Two males, four females)	INF	5–10 mg/kg at weeks 0, 2 and 6, then every 4 weeks	6 months	Improvement to stage I in four cases, stage II in two cases	One with headache
Moriarty et al 2014^Citation31	11 patients (Eight males, three females)	INF	5–10 mg/kg at weeks 0, 2 and 6, then every 4 to 8 weeks	Median 49.1 months	All with initial improvement, two with secondary failure	Nine cutaneous infections requiring antibiotics, four respiratory tract infections requiring antibiotics, one episode of tonsillitis requiring antibiotics, one case of Hodgkin lymphoma 36 months after cessation of INF
Kovacs et al 2018^Citation84	Three (Two males, one female)	GUS	100 mg at weeks 0 and 4, then 8 weekly	At least 12 weeks	Improvements in IHS4, VAS and DLQI at 12 weeks in all patients	None
Weber et al 2017^Citation88	Nine patients (Six males, three females)	APR	30 mg twice daily	2 days to 9 months	Improvement in five of six who persisted with therapy	Two with weight loss, one with loose stool, one with dry cough, one with nausea, one with reflux
Zhang et al 2014^Citation144	22 (nine males, 13 females)	15 on INF, seven on ADA	NR	1 month to 3 years	14 with improvement (11 with INF, three with ADA)	Three with infusion reactions, two with fatigue, one with anaphylaxis, one with heart failure, one with dyspnea, one with recurrent HSV. One death from lung malignancy, one death from metastatic perianal squamous cell carcinoma (both on INF) but no direct causal relationship established.
DeFazio et al 2016^Citation145	11 patients	Eight on INF, three on UST	Mean 10.5 months (6 to 15 months)	NR	Effective in seven, local recurrence in four, of which one was after 4 months of INF	None
Monné et al 2014^Citation146	Four patients	Four on ADA, of which one also tried INF and ETA	Varying doses	NR	ADA effective in three of four, ETA and INF ineffective	None
Gulliver et al 2011^Citation147	Three (one male, two female)	UST	45 mg at 0, 1 and 4 months	6 months	One ineffective, one 25–49% disease clearance, one complete clearance	One patient with S. aureus of right axilla, one patient with cystitis, psoriasiform dermatitis and arthritis
Retrospective analyses
Study	Subject characteristics	Therapies	Dose	Treatment duration	Efficacy	Complications
van Rappard et al 2012^Citation148	30 patients (17 males and 13 females)	INF	Weeks 0, 2 and 6 and subsequently every 8 weeks.	Mean 9.3 months	10 free of lesions, 13 improved, 4 moderately improved, 3 no response	Noted in 12 patients, not further specified
Martin-Ezquerra G et al 2014^Citation149	19 patients (ten males, nine females)	ADA in 11 cases, INF in ten cases, UST in two cases, ETA in two cases**	NR	Mean of 12 months	Physician-judged at least partial responses for ADA in eight, INF in seven, UST in three, none for ETA	Severe infusion reaction and hypertriglyceridemia in two patients
Bettoli, Manfredini et al 2018^Citation150	34 patients (19 males, 15 females)	ADA	NR	Varying, up to at least 1 year	Among group receiving ADA for >1 year, 60% achieved HiSCR at 3 months and maintained up to 12 months.	NR
Kyriakou et al 2018^Citation151	19 (five males, 14 females)	ADA	160 mg at week 0, 80 mg at week 2, 40 mg at week 4 and 40 mg weekly after	At least 24 weeks	63.1% achieved clinical response at 24 weeks (defined by HS-PGA score of clear, minimal or mild with at least two-grade improvement from baseline).	None^#
Casseres et al 2018^Citation85	Eight (five males, three females)	GUS	100 mg at week 0, 4 and then 8 weekly	Up to 10 months	Five (63%) with improvement	None
Cohort studies
Study	Subject characteristics	Therapies	Dose	Treatment duration	Efficacy	Complications
van Rappard et al 2011^Citation152	19 patients (12 males, seven females)	Ten on INF, nine on ADA	INF 5 mg/kg at weeks 0, 2 and 6. ADA 40 mg EOW.	6 weeks	46% reduction in Sartorius score in INF group vs 34% in ADA group	One on INF with acute arthritis and myalgia, three on ADA with fatigue, one with injection site pain
Sbidian et al 2016^Citation153	67 patients (30 males, 37 females)	17 on ADA, 63 on ADA, eight on ETA**	INF 5 mg/kg, ADA 40 mg EOW, ETA 50 mg twice a week	NR	Treatment with ADA associated with at least partial response compared to ETA or INF with hazards ratio of 6.6 (p=0.001)	One each with hepatitis, lupus, repeated urinary tract infection and pulmonary embolism
Shanmugam et al 2018^Citation112	68 patients (23 males, 45 females; 31 ever had biologics, 37 never had biologics)	NR	NR	NR	Ever receiving biologics associated with sharper decline in HS activity, biologic use associated with significant reduction in HSS and Hurley stage, effect of biologics greater in patients who received surgery, combination therapy with surgery and biologics associated with higher probability of achieving 75% reduction in active nodule count.	NR

Clinical trials
Study	Trial characteristics	Subject characteristics	Therapies	Dose	Treatment duration	Efficacy	Complications
Kimball et al 2016,^Citation12 Zouboulis et al 2018^Citation15	Randomized double-blind placebo-controlled Phase III trial, with open-label extension to 168 weeks	307 for PIONEER I, 326 for PIONEER II	ADA	40 mg weekly vs 40 mg EOW vs placebo	36 weeks	More patients in the weekly ADA group achieved HiSCR [41.8% versus 26.0% in PIONEER I (p=0.003) and 58.9% vs 27.6% in PIONEER II (p<0.001)]. Mean duration of infection-free HiSCR was significantly longer in ADA compared to placebo group (p< 0.001).^Citation154 More patients on ADA achieved a ≥30% in the Patient’s Global Assessment of Skin Pain, both PIONEER I (ADA [40.3%] vs placebo [24.9%]; OR =2.03, p=0.004) and II (ADA [61.2%] vs placebo [24.8%]; OR=4.78, p<0.001).^Citation155 Achievement of HiSCR was maintained through week 168 in 52.3% in weekly ADA group and 57.1% of responders plus partial responders.^Citation15	Among ADA group, new psoriasiform eruptions and psoriasis in ten patients, one case of squamous cell carcinoma of the nose, and one death from cardiorespiratory arrest 42 days after the last dose of ADA in a 35-year-old man with a history of diabetes mellitus, smoking and a family history of ischemic heart disease. Adverse events observed during open-label extension were similar to safety profiles observed in PIONEER studies.^Citation15 Safety analysis of every week and EOW dosing showed similar adverse event rates.^Citation16
Jiménez-Gallo et al 2018^Citation156	Prospective open label study	19 (11 males, eight females)	ADA	40 mg weekly	36 weeks	HiSCR in 68.42%.	NR
Kimball et al 2012^Citation11	Phase II parallel randomized, placebo-controlled trial with a blinded 16-week period and an open-label 36-week period	154	ADA	40 mg weekly vs 40 mg EOW vs placebo	52 weeks	17.6% in weekly ADA vs 9.6% in EOW group vs 3.9% in placebo group achieved HS-PGA score of clear, minimal, or mild with at least a two-grade improvement relative to baseline score at week 16 (EOW vs placebo difference, 5.6% [95% CI, 4.0% to 15.3%]; p 0.25; weekly vs placebo difference, 13.7% [CI, 1.7% to 25.7%]; p 0.025). Proportion with clinical response decreased after change from weekly to EOW dosing. A shorter time to achieving HiSCR in weekly ADA vs EOW group.^Citation99	24 listed serious adverse events: rectal fissure, inadequately controlled diabetes mellitus, goiter, hidradenitis, interstitial lung disease, pilonidal cyst, viral infection, anemia, bacteremia, vocal cord neoplasm, bacterial genital infection, Escherichia infection, penile swelling, purulent discharge, pustular rash, scrotal swelling, noncardiac chest pain, and cellulitis.
Arenbergerova et al 2010^Citation157	Open label trial	Eight (three males, five females)	ADA	80 mg at week 0, 40 mg at week 1, then 40 mg EOW	12 months	Mean reduction in pain and discharge of 86.5% and 72.8% respectively at 12 months, and 56.6% and 50.1% at 24 months	One case of EBV infection
Amano et al 2010^Citation101	Open-label Phase II trial	Ten, of which six completed treatment	ADA	160 mg at week 0, 80 mg at week 1, 40 mg EOW	12 weeks	None responded, as defined by at least 50% decrease in HSSI score	No serious adverse events
Leslie et al 2014^Citation60	Open-label trial	6 (Two males, four females), of which five completed the study	ANK	100 mg daily	8 weeks	Significant improvement in modified Sartorius score during treatment and rebound during follow-up post-treatment	None
Tzanetakou et al 2016^Citation58	Randomized double-blind placebo-controlled trial	20 patients (ten in anakinraANK arm, ten in placebo arm), of which 19 completed study	ANK	100 mg daily	12 weeks	At week 12, 78% in ANK arm vs 20% in placebo arm had reduction in disease activity score, defined as the sum of scores of all affected areas (two largest diameters in each affected areas multiplied by degree of inflammation at each lesion), and 78% vs 30% achieved HiSCR. At week 24, 10% vs 33% achieved HiSCR.	No serious adverse events
Vossen et al 2018^Citation89	Randomized double-blind placebo-controlled trial	20 (15 given apremilastAPR and five given placebo) of which 18 completed the study	APR	30 mg BD	16 weeks	Eight of 15 achieved HiSCR in APR arm compared to none in placebo arm (p=0.055) at week 16.	38 adverse events in APR arm vs 11 in placebo arm, none categorized as severe.
Cusack et al 2006^Citation134	Open-label trial	Six	ETA	25 mg twice weekly	17 to 40 weeks	44 to 73% reduction in DLQI 12 to 24 weeks after starting treatment	Increased incidence of URTIs in one patient
Giamarellos-Bourboulis et al 2007^Citation47	Open-label Phase II trial	Ten three males, seven females)	ETA	50 mg weekly	12 weeks	>50% decrease in disease activity (defined as sum of lesions with each lesion evaluated with the formula: lesion diameters multiplied by severity) in six patients at week 12 and seven patients at week 24.	No serious adverse events: three patients with self-limited injection site erythema, one patient with right gluteal abscess
Sotiriou et al 2008^Citation50	Open- label trial	Four (one male and three females)	ETA	25 mg twice a week	6 months	54–73% reduction in DLQI	One case of mild injection site reaction
Lee et al 2009^Citation49	Open-label trial	15, of which ten completed treatment	ETA	50 mg weekly for 12 weeks, then 25 mg weekly for 2 weeks	14 weeks	Only three (20%) of patients achieved 20% reduction in PGA, based on intention to treat analysis.	No serious adverse events reported
Pelekanou et al 2010^Citation48	Open-label Phase II trial	Ten	ETA	50 mg weekly	Initial 12-week duration, then subsequent 0 to 96-week course depending on recurrence	Three who improved in mSS with no recurrence and 7 who improved and then recurred after stopping treatment, of which five had a positive response to repeat treatment	None
Adams et al 2010^Citation51	Randomized trial with 12-week double-blind placebo-controlled phase followed by 12-week open-label phase	20 patients (ten in etanerceptETA arm and ten in placebo arm), of which 14 completed entire study	ETA	50 mg twice weekly	24 weeks	No statistically significant difference in physician global assessment between treatment and placebo arms	No serious adverse events
Paradela et al 2012^Citation33	Open-label trial	Ten (four males, six females)	INF	5 mg/kg at week 0, 2, 6 and then 8-weekly	29 to 181 weeks	Eight with response (defined as 50% reduction in hidradenitis severity score), of which four relapsed (defined as 40% increase in score of initial response)	One case of mycobacterial folliculitis, one case of scrotal abscess, two cases of psoriasis, five cases of positive anti-nuclear antibodies, two cases of transient hyperlipidemia
Grant et al 2010^Citation9	Clinical trial with 8-week double-blind placebo-controlled phase followed by 14- to 22-week open label phase	38 patients (15 in infliximabINF arm and 23 in placebo arm)	INF	5 mg/kg at week 0, 2 and 6 and then 8 weekly	22 weeks	At week 8, 60% of patients in INF arm vs 5.6% of patients in placebo arm had 25% to less than 50% reduction in HSSI, and 13.3% of patients in INF arm vs 88.9% in placebo arm had less than 25% decrease in HSSI (p<0.001).	Serious adverse events: one pregnancy, one case of hypertension, one infusion reaction requiring hospitalization.
Mekkes et al 2007^Citation34	Open-label trial	11, of which ten (four males, six females) completed the study	INF	5 mg/kg at week 0, 2 and 6	6 weeks	Improvements in all patients within 2–6 weeks, as defined by reduction in mSS. At one year, improvements in 6 patients, but recurrences in 4.	One with numbness and pain in both legs, one with anaphylactic shock, and one with myalgia and fever
Kanni et al 2018^Citation66	Randomized double-blind placebo-controlled trial	20 patients (10 in bermekimabBER arm and 10 in placebo arm)	BER	7.5 mg/kg every 14 days	12 weeks	60% in BER arm vs 10% in placebo arm achieved HiSCR at week 12, and 40% vs 0% at week 24.	19 HS exacerbations in BER group, of which 2 required hospitalization
Blok et al 2016^Citation72	Open-label trial	17 (four males, 13 females)	UST	Week 0, 4, 16 and 28–45 mg per dose for participants weighing <100 kg and 90 mg per dose for those >100 kg	28 weeks	Marked improvement of mSS in six (35%), moderate in eight (47%), mild in one (6%), no change/worsening in two (12%) at 40 weeks. Mean mSS of intention-to-treat population decreased from 112.12 to 60.18 at week 40 (46.33% improvement, p<0.01). Eight (47%) achieved HiSCR at week 40.	Headache, fatigue, URTI
Guo et al 2017^Citation91	Open-label phase II trial	12	IFX-1	800 mg on days 1, 4, 8, 15, 22, 29, 36, 43 and 50	50 days	83% achieved HiSCR at Day 134 (95% CI: 0.52–0.98).	NR

Notes: **Overlapping due to switches in therapy. ^#Study excluded patients who discontinued treatment due to adverse event or had to receive another therapeutic modality.

Abbreviations: ADA, adalimumab; GOL, golimumab; ANK, anakinra; ETA, etanercept; INF, infliximab; CAN, canakinumab; RIT, rituximab; SEC, secukinumab; UST, ustekinumab; CER, certolizumab; GUS, guselkumab; APR, apremilast; BER, bermekimab; EOW, every other week; NR, not reported; PASH, pyoderma gangrenosum, acne and suppurative hidradenitis; NSAID, non-steroidal anti-inflammatory drug; HPV, human papillomavirus; SAPHO, synovitis, acne, pustulosis, hyperostosis and osteitis; HCV, hepatitis C virus; Nd-YAG, neodymium-doped yttrium aluminum garnet; CO_2, carbon dioxide; IHS4, international HS severity score system; HSV, herpes simplex virus; HSS, HS score; HiSCR, HS clinical response; URTI, upper respiratory tract infection; PGA, physician global assessment; mSS, modified sartorius score; EBV, Epstein-Barr virus, HSSI, HS severity index.

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