SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• In a phase 2b study (NCT03628924), the percentage of patients who achieved hidradenitis suppurativa clinical response (HiSCR) at week 16 was higher in both TREMFYA groups than in the placebo (PBO) group (TREMFYA 200 mg subcutaneous [SC], 50.8%; TREMFYA 1200 mg intravenous [IV] to 200 mg SC, 45.0%; PBO, 38.7%); the differences between PBO and the TREMFYA groups were not statistically significant (P=0.166 and P=0.459, respectively). At week 40, HiSCRs were 45.8% and 48.3% in the TREMFYA SC and IV groups, respectively, and 46.4% and 53.6% in the PBO→TREMFYA 100 mg and PBO→TREMFYA 200 mg groups, respectively.¹
• In a phase 2a study (NCT04061395) conducted in patients with hidradenitis suppurativa (HS), 65% of patients achieved clinical response after 16 weeks of TREMFYA 200 mg SC.^2,3
• Retrospective studies, case series, and case reports described the use of TREMFYA in patients with HS.^4-12

Clinical data

NOVA

Kimball et al (2023)¹ reported the efficacy, safety, and tolerability of TREMFYA for the treatment of moderate to severe HS in a phase 2, multicenter, randomized, PBO-controlled, double-blind, proof-of-concept study.

Study Design/Methods

• The study design is presented in Figure: NOVA Study Design.
• The primary endpoint was the percentage of patients who achieved HiSCR at week 16. HiSCR was defined as a ≥50% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining fistula count relative to baseline.

Results

• Of the 181 patients who received treatment, the mean age was 38.1 years, and the mean weight was 99.53 kg. Most patients were White (86.8%) and female (63.5%).
• Baseline demographics and clinical characteristics are presented in Table: Baseline Demographics and Clinical Characteristics.

Efficacy

• Primary endpoint was not met for either TREMFYA group; P-values for all major secondary endpoints were considered nominal.
• The results for primary and secondary endpoints at weeks 16 and 40 are summarized in Table: Primary and Secondary Efficacy Results at Weeks 16 and 40.
• Antibodies to guselkumab were detected in 17/147 (11.6%) patients through week 48.
• The incidence of anti-drug antibodies was 15.3% (9/59) and 8.5% (5/59) in the TREMFYA SC and IV groups, respectively.
• No patients developed neutralizing antibodies to guselkumab.

Safety

• Through week 16, serious adverse events (SAEs) were reported in 3 (4.84%) patients in the PBO group (nausea and vomiting [n=1], small intestinal perforation due to an automobile accident [n=1], and tonsillar hypertrophy [n=1]) and 2 (1.7%) patients in TREMFYA groups (1 patient in the TREMFYA 200 mg SC group had anemia and nephrolithiasis, and 1 patient in the TREMFYA 1200 mg IV to 200 mg SC group had cholelithiasis).
• Through week 48, SAEs were reported in 9 patients. The most frequently reported SAEs were gastrointestinal disorders (2 [3.3%] in the TREMFYA IV group; dysphagia [n=1], pancreatitis [n=1]) and skin and subcutaneous tissue disorders (2 [7.1%] in the PBO→TREMFYA 100 mg group [both hidradenitis]).
• Safety events that occurred at weeks 16 and 48 are presented in Table: Key Safety Events at Week 16 and Table: Key Safety Events at Week 48.
• No patients experienced a major adverse cardiovascular event, malignancy, anaphylactic reaction, or serum sickness reaction. No deaths were reported in the study.

HiGUS

Dudink et al (2023)² reported efficacy, safety, tolerability, and mode of action of TREMFYA for the treatment of moderate to severe HS in a phase 2a, multicenter, open-label study.

Study Design/Methods

• The total duration of study was 24 weeks, comprising a 16-week treatment period and an 8-week follow-up period.
• Patients received TREMFYA 200 mg SC at weeks 0 (baseline), 4, 8, and 12.
• Select inclusion criteria: moderate to severe chronic HS for ≥1 year with a history of ≥1 systemic anti-inflammatory/immunosuppressive agent; lesion in ≥2 distinct areas; AN count ≥4; and inadequate response to an adequate course of appropriate oral antibiotics.¹³
• Select exclusion criteria: other active skin condition that could interfere with HS assessments; baseline draining fistula count >20; use of the following therapies before baseline - prescription topicals (within 14 days), systemic nonbiologics (<4 weeks), biologics (within 3 months), oral antibiotics (within 4 weeks), analgesics (within 14 days), systemic immunosuppressants or anakinra (within 4 weeks); prior use of TREMFYA.¹³
• Primary endpoint was changes in inflammatory pathways induced by interleukin (IL)23p19 blockade with TREMFYA from baseline to week 16.³
• Secondary endpoints were inflammatory lesion count and HiSCR, International Hidradenitis Suppurativa Severity Score System (IHS4) and patient-reported outcome measures (PROMs); patient global assessment, numerical rating scales for pain and pruritus, 10-point treatment satisfaction score, and Dermatology Life Quality Index (DLQI).³
• The safety and tolerability of TREMFYA were evaluated based on the incidence of adverse events (AEs) from baseline through week 24.

Results

• Among 20 patients included in the efficacy analyses, mean age was 34.5 years. Most patients were female (65%) and had moderate disease severity (IHS4 score; 55%).
• Efficacy outcomes are presented in Table: Efficacy Evaluations at Week 16.

• The fastest clinical improvement was observed in the first 4 weeks with a significant decrease of 2.23 in IHS4 score (95% confidence interval [CI], -4.26 to -0.20; P=0.033) and 1.76 in AN count (95% CI, -3.24 to -0.28; P=0.022).
• After 16 weeks of treatment, patients who achieved HiSCR showed a statistically significant decrease in DLQI scores compared with those who did not achieve HiSCR (P=0.046). Median patient treatment satisfaction at week 16 was rated as 7/10 (interquartile range [IQR], 5-9).
• Additional primary endpoints on translational outcomes measured using transcriptomic and proteomic methods, and immunochemistry of HS index skin lesions were also reported.

Safety

• A summary of AEs reported during the 24-week study is presented in Table: AEs Reported During 24-Week Study.
• The most common AEs were headache after injection (20%), infection (15%; most frequently upper respiratory tract infections), and nausea (7%).

RETROSPECTIVE STUDIES

Rivera-Díaz et al (2023)⁴ conducted a retrospective, observational, multicenter study in adult patients with moderate to severe HS who were treated with TREMFYA within a compassionate-use program across 13 hospitals in Spain (March 2020-March 2022).

Study Design/Methods

• The study included 69 patients and most patients had Hurley stage III (84.1%), an inflammatory phenotype (61.8%), and a mean of 4.3 affected areas. Approximately 60% of the patients were diagnosed with HS for more than 10 years.
• Overall, 47.5% of the patients had experienced more than 12 HS flare-ups every year and were previously treated with an average of 1.8 biologics, including adalimumab, ustekinumab, and infliximab. The patients had undergone an average of 3.4 surgeries.
• The mean age was 44 years, with 50.7% male and 49.3% female.
• In total, 66.2% of patients received TREMFYA 100 mg at baseline, week 4, and then every 8 weeks (Q8W), 29.4% of patients received TREMFYA 100 mg every 4 weeks (Q4W), and 4.4% of patients received other TREMFYA regimens. Most patients also received other systemic therapies such as doxycycline, metformin, and dapsone.
• The change in IHS4, HS- physical global assessment (HS-PGA), Numerical Pain Rating Scale (NPRS), and DLQI scores between baseline and treatment week 4, 16, 24, and 48 were determined.
• The clinical characteristics related to attainment of HiSCR, 55% reduction in IHS4 (IHS4-55), and minimum clinically important difference (MCID) in DLQI at weeks 16 and 24 were evaluated.

Results

• A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores from baseline was observed at weeks 16, 24, and 48 (P<0.0001).
• The changes in clinical parameters from baseline to week 48 are presented in Table: Changes in IHS4, HS-PGA, NPRS, and DLQI Scores from Baseline to Week 48.

• The percentage of patients who achieved HiSCR, IHS4-55, MCID in DLQI (≥4-point reduction in DLQI), and an NPRS score <3 is presented in Table: Percentage of Patients Achieved HiSCR, IHS4-55%, DLQI 4p, NPRS score <3 in Week 16 And Week 24.

• Association between TREMFYA 100 mg Q4W and HiSCR achievement (odds ratio [OR], 0.15; 95% CI, 0.04-0.56; P=0.004) was statistically significant at week 16 but not at week 24.
• The probability of a decrease in DLQI ≥4 points (MCID) at week 16 was lower in males (OR, 0.11; 95% CI, 0.02-0.58; P=0.009) and among those who had received a higher number of biologics (OR, 0.29; 95% CI, 0.09-0.88; P=0.029).
• NPRS <3 points was significantly more difficult to achieve among patients who were administered a higher number of biologics (OR, 0.34; 95% CI, 0.13-0.84; P=0.020) at week 16 and who had a higher number of fistulas (OR, 0.68; 95% CI, 0.74-0.99; P=0.046) at week 24.
• A correlation between larger number of body areas affected and less probability to obtain an NPRS score <3 was observed at both week 16 (OR, 0.65; 95% CI, 0.44-0.96; P=0.033) and week 24 (OR, 0.67; 95% CI, 0.44-0.99; P=0.049).
• TREMFYA was discontinued in 16 patients (23.2%), following a mean treatment duration of 7.81 months. Inefficacy or loss of efficacy (62.5%) was the most common reason for discontinuation. 39 patients (56.5%) reached 48 weeks of treatment with TREMFYA.
• A total of 7 AEs were reported, and no SAEs were observed.

Melgosa Ramos et al (2022)⁵ conducted a retrospective, bicentric study in Spain including 11 patients with moderate to severe HS who were treated with TREMFYA.

Study Design/Methods

• The study included 11 patients with a Hurley Stage of II or III, 9.1% and 90.9%, respectively.
• Patients ranged in age from 24-61 years old with a male to female ratio of 4:7.
• Dose intensification options included TREMFYA 200 mg and/or TREMFYA 100 mg every 6 weeks.
• All patients were previously treated with biologics (adalimumab [n=9], ustekinumab [n=6], secukinumab [n=2], etanercept [n=1]) before receiving TREMFYA.
  • Six patients (54.5%) had previously received 2 or more biologic treatments.
• The average IHS4 score was 13.27 ± 4.67 before treatment with TREMFYA.
• The primary endpoint was evaluated at week 16 ± 4 weeks of follow-up and consisted of the percentage of patients achieving HiSCR, PGA <2, and clinical response maintenance during the evaluated period.

Results

• The mean follow-up was 24.54 ± 31.86 months with a range of 1-112 months.
• At week 16, 7 patients (63.6%) achieved the primary endpoint, and they all received TREMFYA 100 mg SC at week 0, week 4, and Q8W.
  • It was necessary to increase the frequency of administration to TREMFYA 100 mg every 6 weeks in 6 out of the 7 patients (72.7%).
• Three of the patients received a dose intensification to TREMFYA 200 mg.
• Four patients had to discontinue TREMFYA (2 due to primary failure despite dose and/or frequency intensification, 1 due to spondylarthritis, and 1 due to a severe infection).
• None of the patients with adverse effects were intensified in dose or frequency.

Casseres et al (2018)⁶ described a retrospective chart review of 8 patients with moderate to severe HS who were treated with TREMFYA 100 mg SC at week 0, week 4, and Q8W thereafter.

Patient Characteristics

• Four of the patients had comorbid psoriasis (PsO), with 3 starting TREMFYA for PsO.
• One patient developed HS after starting an anti-IL-17 agent.
• Patients ranged in age from 15-68 years old, with an average weight of 98 kg and 5 patients (63%) were male.
• Four patients (50%) had Hurley stage III disease and 4 (50%) had Hurley stage II disease.
• Seven patients (88%) were previously treated with biologics (adalimumab [n=5], secukinumab [n=4], ixekizumab [n=2], and ustekinumab [n=1]).
• Five patients had prior treatment with oral antibiotics and 2 patients with isotretinoin.
• Three patients continued antibiotics while on TREMFYA.

Results

• After treatment with TREMFYA, 5 patients (63%) reported improvement in their HS and 1 patient’s HS remained quiescent.
• Three patients who eventually improved did not show improvement at 2-4 months.

CASE SERIES

Montero-Vilchez et al (2020)⁷ described the use of TREMFYA in a case series of patients with HS previously treated with other biologic therapy.

• A total of 4 patients were included in this study, the mean age was 41.5 years; 3 patients were smokers, and 2 were obese.
• Previous biologic therapy included adalimumab and ustekinumab in all patients, infliximab in 3 patients, and secukinumab in 1 patient.
• TREMFYA 100 mg SC was administered at week 0 and Q4W.
• At week 12, slight improvement was observed in 2 patients (moderate reduction in IHS4 score, the visual analog scale [VAS] for pain, and the DLQI); none of the patients improved their HS-PGA score, and 1 patient had increased HS severity.
• There were no drug-related AEs.

Kovacs et al (2018)⁸ described the use of TREMFYA in 3 patients with severe HS (Hurley stage III) who responded poorly to other treatments or had exclusion criteria for the use of adalimumab.

• The 3 patients were not able to be treated with adalimumab due to: one patient with a poor response of HS to weekly administered adalimumab despite achieving a ≥70% improvement in Psoriasis Area Severity Index score (PASI 70) for concomitant severe PsO; the second patient refusing to receive weekly injections due to injection phobia; and the third patient was unable to receive tumor necrosis factor (TNF)-alpha inhibitors due to unclear history of systemic lupus erythematodes.
• Patients were treated with TREMFYA according to the plaque PsO dosing with TREMFYA 100 mg administered SC at weeks 0 and 4 (induction phase) and Q8W thereafter (maintenance phase).
• Treatment was assessed using the IHS4, the VAS for pain, and the DLQI scores before therapy and at week 8 and week 12 after induction.
• All patients were previously treated with topical therapy, clindamycin, and rifampicin. Additionally, 1 patient had received previous treatment with adalimumab as previously mentioned.
• Description of patient characteristics and response to therapy are summarized in Table: Patient Characteristics and Response to Therapy.

• No AEs were reported.

Case reports

Berman et al (2021)⁹ describe a case report of a 28-year-old female patient with HS (Hurley stage II), PsO, and Crohn’s disease.

Patient Characteristics

• Diagnosis of HS (Hurley stage II) took place at the age of 13, PsO at the age of 24, and Crohn’s disease at the age of 25.
• The patient failed disease specific treatments such as antibiotics for HS, phototherapy for PsO, and several biologic agents as summarized in Table: Biologic Treatment Course.

• Prior to TREMFYA initiation, the patient’s HS was being treated with doxycycline for over 2 months without benefit.
• HS was active with >10 inflammatory nodules and abscesses on the groin, buttocks, hips, inner thighs, and lower abdomen. Lymphedema of the mons pubis and labia majora were also present. Upon examination, non-draining sinus tracts and scarring of the bilateral axillae were also seen.
• TREMFYA was initiated 2 weeks after discontinuation of infliximab using a dosing regimen of 100 mg at baseline, week 5, week 12, and week 20.

Results

• Clinical responses to TREMFYA treatment by disease state at weeks 0, 5, 12, and 20 are summarized in Table: Clinical Response.

• A minor HS flare with 3-4 new inflammatory nodules occurred at week 18. A 2-week course of cephalexin was initiated, and the patient went back into remission.
• Patient was instructed to increase TREMFYA to every 6 weeks if flare ups occur at end of injection cycle.
• At week 28, the patient’s HS, PsO, and Crohn’s disease are all in remission.

Burzi et al (2021)¹⁰ described a case report of a 45-year-old female with HS localized on axilla and groins bilaterally for 20 years (Hurley stage III).

Patient Characteristics

• The patient presented with a total of 7 draining fistulas on the right and left axillary areas with an abscess on the left axilla and multiple nodules. She also had 3 draining fistulas and 1 inflamed nodule in the left groin and multiple non-inflamed nodules on the right thigh (IHS4 score: 50). The lesions were painful (VAS score: 9) and had a negative impact on her quality of life (DLQI score: 18). Vulgar PsO with palmar involvement was also observed.
• She had been previously treated with adalimumab 40 mg weekly with initial partial improvement.
• The patient was started on TREMFYA 100 mg SC at weeks 0 and 4 and Q8W thereafter.
• After 4 months of treatment with TREMFYA, there were no active fistulas nor abscesses on the axillary areas bilaterally with a single draining fistula on the left groin (IHS9). Reduction of the inflammatory and exudative components and complete regression of psoriasiform lesions were also observed. The patient did not report painful symptoms (VAS score: 0) and improvement in her DLQI score was noted (DLQI score: 6).

Jorgensen et al (2020)¹¹ describe a case report of a 25-year-old male patient with HS (Hurley stage II) and Crohn’s disease.

Patient Characteristics

• Patient presented with lesions in the groins and anogenital skin.
• Patient had HS (Hurley stage II) since 2016 and Crohn’s disease since 2014. Patient also had a family history of HS.
• In August 2017, patient had a DLQI score of 8 (range scale 0-30, with high score indicating worse quality of life), an overall disease bother score and overall disease pain score on a VAS of 6.8 and 7.6, respectively, out of 10.
• Over the course of 19 months, his HS worsened with treatments including systemic tetracycline, doxycycline, rifampicin/clindamycin, adalimumab, and ustekinumab and several surgical interventions.
• TREMFYA was initiated in April 2019 using the dosing regimen of 100 mg at week 0, 100 mg at week 4, and 100 mg Q8W thereafter. After 6 months, maintenance dosing was increased to 100 mg every 6 weeks.
• In January 2020, excision of a fistula was performed by plastic surgeons.

Results

• After 7 months of TREMFYA initiation, patient experienced a subjective improvement.
• In March 2020, patient reported a reduction in number of boils in the preceding month to 0, in DLQI to 1, in overall disease bother score to 2.2, and in HSS to 5.
• In May 2020, patient’s HS remained in remission with treatment of TREMFYA 100 mg every 6 weeks.
• During the treatment period of 12 months with TREMFYA, patient experienced occurrence of 2 inflamed nodules, which were treated with triamcinolone injections.
• Patient also had an episode of fever and abdominal pain after alcohol intake, which resulted in a 2-week postponement of TREMFYA injection.

Kearney et al (2020)¹² describe a case report of a 28-year-old female patient with HS (Hurley stage III).

• Patient presented with inflammatory nodules, abscesses, and confluent, actively draining tracts, and scarring in the axillae along with scarring in the groin and on the buttocks (HS, Hurley stage III).
• Past medical history was significant for latent pulmonary tuberculosis treated with 6 months of rifampicin.
• Patient had no prior smoking history and a normal body mass index, weighing 65.5 kg at presentation.
• Human immunodeficiency virus and hepatitis serology were negative.
• Varicella immunity was confirmed and a QuantiFERON test was positive.
• Metformin 500 mg once daily increased to 1000 mg twice daily as tolerated with spironolactone 100 mg once daily was initiated.
• Four weeks after metformin and spironolactone initiation, patient had 16 seton sutures inserted in the axillae.
• After 12 weeks of treatment with metformin and spironolactone, TREMFYA 100 mg SC at week 0, week 4, and then Q8W thereafter was initiated.
• At week 12 of TREMFYA treatment, significant improvement in pain and a resolution of all active inflammatory nodules, abscesses, and draining fistulae were reported.
• Metformin and spironolactone were discontinued.
• At week 24 of TREMFYA 100 mg Q8W treatment, patient’s HS remains in remission.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 09 May 2024.