Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• There are data available from a randomized study¹ and prospective studies^2-4, that described the use of REMICADE in patients with hidradenitis suppurative (HS).

CLINICAL DATA

Controlled Study

Grant et al (2010)¹ reported the results of a single-center, prospective, randomized, double-blind, placebo-controlled, open-label, crossover study that evaluated the use of REMICADE in patients with moderate to severe HS with follow-up through week 52.

Study Design/Methods

• Patients were randomized to receive REMICADE 5 mg/kg or placebo on weeks 0, 2, and 6. After week 8, patients in the placebo group were given the opportunity to crossover to the REMICADE group to receive REMICADE 5 mg/kg at weeks 8, 10, and 14, and every 8 weeks thereafter until week 30.
• Patients initially randomized to treatment with REMICADE received additional doses every 8 weeks through week 22. This second phase was followed by a third phase which began on week 22 (REMICADE group) or week 30 (placebo crossover to REMICADE group) through week 52. Patients did not receive REMICADE treatment during this phase.
• The study included patients who were ≥18 years of age with moderate to severe HS (Hidradenitis Suppurativa Severity Index [HSSI]>8), and at least 1 of the following:
  • A history of HS for at least 1 year with multiple emergency room or doctors’ visits related to HS
  • Intralesional steroid injection >5 per year (not within 2 weeks of entry)
  • ≥1 previously failed course of antibiotic therapy that was not administered within 2 weeks of study entry (excluding antibiotics given for active infection immediately before randomization)
  • Failed systemic retinoids or a history of reconstructive surgery that was not within 3 months prior to study entry
• The primary endpoint of the study was the proportion of patients with ≥50% reduction from baseline in the HSSI score at week 8. The score ranges from 0-19 (higher numbers reflect greater severity of the disease) and consists of 2 static components (body surface area and the number of sites involved) and 3 dynamic components (number of active lesions, pain by visual analogue scale [VAS], and changes of dressing during working hours).
• Secondary endpoints included changes from baseline for VAS, Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein level (CRP).

Results

• Fifteen patients were randomized to REMICADE, and 23 patients to placebo (however, only 18 placebo patients were included in efficacy analyses).
• In the REMICADE group, 73% continued study participation through week 22 and 20% (n=3) of these patients continued to week 52.
• More patients in the REMICADE group experienced a ≥50% reduction in HSSI at week 8 compared with the placebo group (P=0.092). Significantly more REMICADE-treated patients (60%) responded with a 25% to <50% decrease in HSSI than placebo patients (5.6%). On the other hand, more placebo patients (88.9%) had a <25% decrease in HSSI from baseline than REMICADE-treated patients (13.3%; P<0.001).
• At week 8, the mean change in DLQI from baseline was 10.0 in the REMICADE-treated patients, and 1.6 in the placebo patients (a mean change of 5 reflects a clinically meaningful improvement; P=0.003). A significantly greater improvement in the mean VAS change from baseline was observed in the REMICADE-treated patients (39.8) than the placebo patients (0.6; P<0.001). Mean PGA scores were significantly lower in the REMICADE-treated patients compared with the placebo group (1.8 vs 4.7; P<0.001), respectively.
• A significant improvement from baseline of markers of inflammation including CRP and ESR was reported in the REMICADE-treated patients compared to the placebo patients.
• There were 5 patients (3 REMICADE, 2 placebo) who were followed through week 52. Based on HSSI, DLQI, VAS, PGA, CRP, and ESR scores, 3 patients required continued treatment with REMICADE to maintain response, and 2 patients experienced a more protracted response. Many patients withdrew before the observation period.
• In the original REMICADE group (n=15), adverse events (AEs) were mild and included headache, dizziness, myalgia, and influenza-like illness. There were no infusion reactions reported in this group. In the placebo patients who crossed over to the REMICADE group, 4 patients (22%) experienced infusion reactions and withdrew from the study.
• Serious AEs in the original REMICADE group included a pregnancy that resulted in study withdrawal and a case of hypertension. In the placebo crossover group, serious AEs included an infusion reaction that resulted in hospitalization and study withdrawal.

Prospective Studies

Ghias et al (2020)² evaluated the efficacy of high-dose and high-frequency REMICADE in a prospective cohort study of 42 patients with HS.

Study Design/Methods

• Clinical cohort included patients at Montefiore Medical Center with a diagnosis of HS and REMICADE treatment from March 2018 through February 2019 who fulfilled the following diagnostic criteria for HS: history of recurrent painful and/or purulent lesions localized to apocrine gland-bearing skin (at least twice in the last 6 months) and clinical presentation of nodules, abscesses, cysts, tunnels, and/or scarring of intertriginous area.
• REMICADE treatment was initiated with an induction dose of 7.5 mg/kg at weeks 0, 2, and 6, followed by a maintenance dose of 7.5 mg/kg every 4 weeks (Q4W).
• Patients with inadequate disease control (HS Physician Global Assessment [HS-PGA] score ≥3) after completion of induction dose would receive dose escalation at 10 mg/kg.
• Efficacy was evaluated at weeks 4 and 12 and based on HS-PGA (range, 0-5) and Numerical Rating Scale (NRS) for pain (range, 0-10).
• The primary outcome was the proportion of patients with successful clinical response, defined by HS-PGA of clear, minimal, or mild (score of 0-2) and at least a 2-grade improvement from baseline.
• Secondary outcomes were the proportion of patients with HS-PGA score of 0-2 at weeks 4 and 12; mean HS-PGA score and mean NRS pain score at weeks 0, 4, and 12; and the proportion of patients achieving a minimum clinically important difference (MCID) in NRS pain scores at weeks 4 and 12.
• Serious adverse events (SAEs) were assessed by reviewing patient and infusion center notes.

Results

• Forty-two patients who were REMICADE-naïve received 7.5 mg/kg Q4W and 24 of these patients completed the week 12 follow-up.
• Sixteen patients with inadequate disease control with REMICADE 7.5 mg/kg Q4W received REMICADE escalation at 10 mg/kg Q4W and 12 of these patients completed the week 12 follow-up.

Efficacy

• Among patients receiving REMICADE 7.5 mg/kg Q4W, significant reduction in HS-PGA score was observed from week 0 to 4 (n=42) and from week 4 to week 12 (n=24; P<0.001, respectively).
• The proportion of patients with achieving clinical responses were 47.6% (20/42) at week 4 and 70.8% (17/24) at week 12.
• Within 4 weeks of initiating REMICADE 7.5 mg/kg Q4W, 28 of 48 patients had complete resolution of pain.
• Among patients who were escalated to REMICADE 10 mg/kg Q4W after inadequate control on REMICADE 7.5 mg/kg Q4W, HS-PGA score significantly decreased from week 0 to week 4 (P<0.001) and improvement was sustained at week 12.
• The proportion of patients with achieving clinical responses were 37.5% (6/16) at week 4 and 50.0% (6/12) at week 12.
• Significant reduction in NRS pain score was observed from week 0 to 4 in patients receiving REMICADE 7.5 mg/kg Q4W (P<0.001) and in patients who were escalated to REMICADE 10 mg/kg Q4W after inadequate control on REMICADE 7.5 mg/kg Q4W (P=0.002), with sustained efficacy at week 12 in both cohorts.
• Secondary efficacy outcomes of both cohorts are summarized in Table: Secondary Efficacy Outcomes in Patients Receiving REMICADE 7.5 mg/kg Every 4 Weeks Cohort and REMICADE 10 mg/kg Every 4 Weeks Cohort.

Safety

• No known SAEs were identified from medical records of patients included in this study.
• Treatment discontinuation was reported in one patient due to myalgia and influenza-like symptoms.

Paradela et al (2012)³ conducted a long-term (2007-11), prospective, open, uncontrolled study of 10 patients with moderate to severe HS treated with REMICADE.

Study Design/Methods

• The study population included patients who were older than 18 years of age, with Hurley stages II-III  for at least 6 months that was refractory to other medical therapies and intralesional steroid injection. Multiple anatomical regions needed to be involved, so HS could not easily be cured by surgical treatment or a history of failed treatment by carbon dioxide laser or surgical drainage.
• Patients were excluded if they had opportunistic infections, poorly controlled medical conditions, active tuberculosis, history of lymphoproliferative disease or other malignancies, human immunodeficiency virus, hepatitis B or C infection, or were pregnant, planning to become pregnant, or lactating.
• REMICADE 5 mg/kg was administered over 4 hours at weeks 0, 2, 6, and then every 8 weeks.
• Objective clinical assessment of disease severity (using Hurley staging system) and activity (using hidradenitis suppurativa score [HSS]) and static PGA in each patient was conducted by 2 physicians at weeks 0, 6, 13, and every 8 weeks thereafter.
• Efficacy was based on response (at least 50% decrease from baseline in HSS after starting REMICADE) and relapse (an increase of 40% of the initial response achieved).
• Safety was assessed based on clinical AEs (reported by the patient or observed during clinical visits or REMICADE infusions) and laboratory test results.

Results

• Two patients discontinued treatment after 5 doses (lack of response).
• The time to response in the 8 responders ranged from 13-45 weeks, and 3-7 doses of REMICADE.
• Relapse occurred in 50% of patients after a median disease-free period of 16 weeks. Only 1 patient recovered initial response after relapse.
• No infusion reactions or life-threatening AEs were detected. Psoriasis occurred in 2 patients, both having a family history of disease. There was a positive antinuclear antibody (ANA) test in 5 patients without the presence of lupus syndrome, and transient hyperlipidemia in 2 patients.
• REMICADE was discontinued due to AEs in 2 patients (mycobacterial folliculitis and scrotal abscess swelling that required surgical debridement).

Lesage et al (2012)⁴ conducted a prospective, single-center, interventional study of 10 patients (median age 39 years) with moderate to severe HS treated with REMICADE from April 2009 to August 2011.

Study Design/Methods

• Patients with active moderate to severe HS, with Hurley score ≥II and not eligible for surgery (early relapse following extensive surgery, multifocal involvement) were included.
• Patients with a contraindication to treatment with an anti-tumor necrosis factor agent were excluded.
• All patients failed 2 or more systemic agents and had undergone several extensive surgeries.

Results

• REMICADE 5 mg/kg was administered at weeks 0, 2, and 6, and then every 4 weeks as maintenance. With a satisfactory response, further spacing of infusions was attempted from the fourth month. Only 1 patient was able to receive infusions at 8-week intervals without flares. All other patients experienced new flares if doses were spaced beyond a 5-week interval.
• Complete efficacy was obtained for 2 patients and partial efficacy for 8. Eight patients were treated with REMICADE for 1 year.
• Over 12 months, the mean number of involved sites decreased from 5 to 1 (P<0.001) after starting REMICADE.
• The number of annual flares declined from a mean of 24 to 6 over 12 months (P<0.05).
• The severity of HS decreased quickly for all patients, with 5 patients achieving Hurley score of 1 at 6 months and 8 patients at 9 months. The improvement was sustained over time with similar results at 12 months.
• The number of associated medications for flare treatment decreased over the year from a mean of 5 to 2.
• AEs reported during the study included 4 minor infections, 1 keratoacanthoma, and
  1 rapidly resolving drug-induced hepatitis.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent^® (and/or other resources, including internal/external databases) was conducted on 04 April 2023.