Comparing the Effectiveness and Safety Associated With Infliximab vs Infliximab-abda Therapy for Patients With Hidradenitis Suppurativa

Key Points

Question

Are infliximab-abda and infliximab therapies associated with similar clinical responses in the treatment of hidradenitis suppurativa?

Findings

In this cohort study that included 34 adults, the proportions of patients in the infliximab-abda (71%) and infliximab (60%) treatment groups achieving a Hidradenitis Suppurativa Clinical Response were not significantly different.

Meaning

Infliximab-abda is a potential alternative to infliximab for treatment of hidradenitis suppurativa.

Abstract

Importance

Although limited effective and affordable treatment options exist for hidradenitis suppurativa, recent studies describe the effectiveness of a medical therapy, infliximab, for the treatment of hidradenitis suppurativa. Cost-saving biosimilar alternatives have recently become available, but no data currently exist on their safety and effectiveness.

Objective

To evaluate the effectiveness of infliximab-abda vs infliximab administration associated with the treatment of hidradenitis suppurativa.

Design, Setting, and Participants

This retrospective cohort study identified patients treated with infliximab or infliximab-abda between 2016 and 2020 at the dermatology clinic at the University of North Carolina at Chapel Hill. The study population included patients who met the clinical criteria for hidradenitis suppurativa and had received a continuous dose of infliximab or infliximab-abda for at least 10 weeks. In total, 62 potential participants were identified using clinical tracking lists on the electronic medical records, and 34 participants were included in the final analysis.

Exposures

Patients who started receiving infliximab or infliximab-abda were clinically tracked for a minimum of 10 weeks using the electronic medical record system, beginning at the time of drug initiation. Patients received loading doses of 10 mg/kg at weeks 0, 2, and 6, and then treatment was continued with a maintenance dose administered every 4 to 8 weeks.

Main Outcomes and Measures

The primary outcome measure was Hidradenitis Suppurativa Clinical Response, defined as at least 50% decrease in inflammatory nodule count without any increase in number of abscesses or draining sinuses.

Results

Of 34 participants, 20 comprised the infliximab treatment group (mean [SD] age, 42.2 [13.2] years; 17 women [85%]), and 14 comprised the infliximab-abda treatment group (mean [SD] age, 35.5 [10.9] years; 13 women [93%]). The proportions of patients achieving a Hidradenitis Suppurativa Clinical Response were 71% (10 patients) in the infliximab-abda and 60% (12 patients) in the infliximab treatment group, which were not significantly different (P = .47).

Conclusions and Relevance

This cohort study found that both infliximab administration and infliximab-abda administration were associated with similar and significant improvement in disease as measured by the Hidradenitis Suppurativa Clinical Response. Infliximab-abda is likely a reasonable treatment option for hidradenitis suppurativa, and further research is warranted.

This cohort study assesses whether infliximab-abda and infliximab therapies are associated with similar clinical responses in the treatment of adults with hidradenitis suppurativa.

Introduction

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition.¹ Symptom onset typically occurs in the third and fourth decades of life.² The prevalence of HS is estimated to be 0.05% to 4.00% of the population.³ Women are 3 times as likely as men to be affected, and Black individuals are more likely than other races/ethnicities to be affected.⁴ Despite HS being chronic and severe with clear diagnostic criteria, diagnostic delay and misdiagnosis are frequent.^5,6

Current treatment options include surgery, laser treatment, antibiotics, and immunomodulator therapies.⁷ Surgical intervention, in addition to medical management, is frequently needed.^8,9 The tumor necrosis factor α inhibitor, adalimumab, is the only drug currently approved by the US Food and Drug Administration (FDA) for HS.³ Another tumor necrosis factor α inhibitor, infliximab (IFX), appears to be effective based on limited data^8,10,11 and frequently is used off-label in clinical practice. Cost-saving biosimilar alternatives have recently become available, although, to our knowledge, no data exist on their safety and efficacy for treating HS. Practically, patients often cannot obtain insurance coverage or access manufacturer assistance programs that ensure affordability for biosimilars, which may lead to the use of the more expensive proprietary drug. To address this issue, the present retrospective cohort study compared the effectiveness and safety of the infliximab biosimilar, infliximab-abda (IFX-A), with the effectiveness and safety of IFX for treating HS. The US FDA has approved IFX-A for treatment of other inflammatory disorders, including Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Infliximab and IFX-A have similar response rates in treating rheumatoid arthritis.¹² Another IFX biosimilar, infliximab-dyyb, has shown no significant difference compared with IFX in the effectiveness of treatment of inflammatory bowel disease, rheumatoid arthritis, or ankylosing spondylitis.¹³

Methods

This retrospective cohort study of 34 patients evaluated the effectiveness and safety associated with IFX-A vs IFX therapy for the treatment of HS. The University of North Carolina (UNC) at Chapel Hill institutional review board approved the study procedures and waived the requirement for obtaining informed consent given the minimal risk associated with data collection by review of medical records. No one received compensation or was offered any incentive for participating in this study.

Study participants were drawn from a dermatology specialty clinic at UNC at Chapel Hill. Participants were given IFX or IFX-A based primarily on financial considerations and insurance coverage to minimize out-of-pocket costs for patients and were included in the study if they received a continuous dose of IFX or IFX-A for at least 10 weeks. Patients were excluded if they received IFX or IFX-A for less than 10 weeks or if the primary outcome, Hidradenitis Suppurativa Clinical Response (HiSCR), was not measurable based on available data. In total, 62 potential participants were identified via clinical tracking lists in the electronic medical record (EMR). Of the potential participants, 6 were excluded owing to never beginning infusions, 1 for receiving IFX prior to visiting UNC, 8 for receiving treatment for less than 10 weeks, and 13 for not having data available for HiSCR measurement. The final analysis included 34 patients. Of the 8 patients not included owing to receiving treatment for less than 10 weeks, 3 were currently receiving IFX or IFX-A at the time of data collection but had begun treatment too recently to be included, 1 patient stopped treatment owing to insurance coverage problems, 1 had a severe adverse infusion reaction, 1 stopped owing to inadequate improvement, and 2 stopped for unknown reasons. Two patients from the IFX treatment group and 3 patients from the IFX-A treatment group stopped treatment prior to 10 weeks.

Patients receiving IFX or IFX-A were clinically tracked using the EMR beginning at the time of drug initiation. Two patients received a loading dose of 7.5 mg/kg, but most received a loading dose of 10 mg/kg at weeks 0, 2, and 6 and received maintenance doses ranging from every 4 weeks to every 8 weeks as described in recent reports.^10,14 Patients typically started receiving the maintenance dose at 8 weeks, but the interval was decreased to optimize the response if the patient experienced HS flares prior to the next dose or achieved an inadequate response.

Data on age, demographic characteristics, symptoms, Hurley stage, laboratory values, medication regimen, clinical findings, and patient-reported outcomes were collected for each patient between February 2016 and June 2020 and retrieved via EMR review. The aforementioned categories were compared before and after the use of IFX or IFX-A. Primary and secondary end points were measured at the patient’s initial visit and at the patient’s most recent visit.

The primary outcome measure used was HiSCR, which was defined as at least a 50% decrease in inflammatory nodule count without any increase in the number of abscesses or draining sinuses, and was determined using data collected from each patient’s initial visit and final available time point. Secondary outcomes included International Hidradenitis Suppurativa Severity Scoring System (IHS4) score, Dermatology Life Quality Index (DLQI), visual analog scale pain scores, and laboratory values, such as hemoglobin level, hematocrit, C-reactive protein level, and erythrocyte sedimentation rate. In our subspecialty clinic, lesion counts, DLQI, and visual analog scale pain scores were recorded routinely at each visit.

Statistical analysis was performed in Microsoft Excel, 2019 version, and included 1-tailed and 2-tailed t tests and χ² analyses to assess differences between IFX and IFX-A; P < .05 was considered statistically significant. Noninferiority criteria included being within a 95% CI as well as achieving at least 75% of the same clinical improvement experienced by the IFX group.

Results

Of 34 patients included in the analyses, 20 comprised the IFX treatment group (mean [SD] age, 42.2 [13.2] years; 17 women [85%]), and 14 comprised the IFX-A treatment group (mean [SD] age, 35.5 [10.9] years; 13 women [93%]). No significant differences in demographic characteristics or clinical outcomes were found between the treatment groups (Table 1). Both treatments were associated with statistically significant improvements in IHS4 scores and DLQI values that were not statistically significantly different between treatment groups (Table 2). The only category that differed between the groups was the mean visual analog scale pain score; the IFX group had a statistically significant difference in mean scores between the initial and final available visits (6.12 vs 4.00; 95% CI, 4.12-5.94; P = .03), whereas the IFX-A group did not (6.82 vs 6.00; 95% CI, 4.36-6.38; P = .49). Both IFX therapy and IFX-A therapy were similar with regard to changes associated with hemoglobin level, C-reactive protein level, and erythrocyte sedimentation rate, with no statistically significant difference between the groups (Table 2). The proportion of patients achieving a HiSCR response was 71% (10 of 14) in the IFX-A treatment group and 60% (12 of 20) in the IFX treatment group, which was not a statistically significant difference (P = .47).

Table 1. Patient Demographic and Clinical Characteristics.

Characteristic	No. (%) of patients		P value
	IFX-A (n = 14)	IFX (n = 20)
Age, mean (SD), y	35.5 (10.9)	42.2 (13.2)	.12
Sex
Male	1 (7)	3 (15)	.24
Female	13 (93)	17 (85)	.17
Race/ethnicity
Black	8 (57)	14 (70)	.35
White	5 (36)	6 (30)	.23
Other	1 (7)	0	.19
Smoking history	4 (29)	4 (20)	.32
BMI, mean (median)	39.96 (34.73)	37.20 (34.82)	.51
Hurley stage
I	0	0
II	3 (21)	2 (10)	.48
III	11 (79)	18 (90)	.59

Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); IFX, infliximab; IFX-A, infliximab-abda.

Table 2. Clinical and Laboratory Values Before and After Treatment, by Treatment Group.

Measure	IFX-A (n = 14), mean		P value	95% CI	IFX (n = 20), mean		P value	95% CI
	Before treatment	After treatment			Before treatment	After treatment
DLQI score	22.64	17.17	.04	16.63-22.36	22.19	16.38	.02	16.89-21.95
IHS4 score	21.36	6.86	.004	8.82-19.40	23.70	10.80	.01	12.36-22.17
VAS pain score	6.82	6.00	.49	4.36-6.38	6.12	4.00	.03	4.12-5.94
HiSCR, No. (%)	NA	10 (71)	NA	NA	NA	12 (60)	.47	NA
AN count	14.43	4.78	.005	NA	14.55	6.85	<.001	9.06-13.10
Hemoglobin, g/dL	11.86	12.36	.44	11.48-12.74	11.34	11.86	.36	11.04-12.14
Hematocrit, %	36.88	38.35	.38	36.01-39.21	36.13	37.08	.54	35.11-38.07
ESR, mm/h	50.50	46.77	.82	33.70-56.83	62.47	54.31	.49	47.20-69.82
CRP, mg/dL	28.99	17.69	.24	13.07-24.89	31.27	21.38	.58	16.16-30.35

Abbreviations: AN, inflammatory nodule; CRP, C-reactive protein; DLQI, Dermatology Life Quality Index; ESR, erythrocyte sedimentation rate; HiSCR, Hidradenitis Suppurativa Clinical Response; IHS4, International Hidradenitis Suppurativa Severity Scoring System; IFX, infliximab; IFX-A, infliximab-abda; NA, not applicable; VAS, visual analog scale.

SI conversion factors: To convert hemoglobin to grams per liter, multiply by 10.0; hemoglobin to proportion of 1.0, by 0.01; CRP to milligrams per liter, by 10.0.

Three patients in the IFX group experienced adverse events; the IFX-A treatment group reported no adverse events. Two patients stopped treatment owing to an infusion reaction and elevated liver enzymes, and a third patient temporarily stopped treatment owing to concern for drug-induced lupus but later restarted IFX.

Discussion

This study provides valuable data for administration of IFX and IFX-A in treating HS. The significant and similar improvements associated with primary and secondary outcome measures in patients treated with IFX and IFX-A are consistent with those in previous studies of IFX administration for treatment of HS.^10,15 In addition, the response rates associated with treatment in this study were slightly higher than those shown in the PIONEER trials for adalimumab (a phase 3 multicenter study of the safety and efficacy of adalimumab in subjects with moderate to severe hidradenitis suppurativa).⁷ Overall, treatment with IFX or IFX-A in the present study was associated with good tolerance and clinical response for most of the participants.

Limitations

Our results are limited by small sample sizes, the retrospective nature of the data, and the use of concomitant medications by some participants. There is also a risk of selection bias because copay and medication assistance programs are not available for IFX-A for patients with HS. Despite this, the population characteristics in the 2 treatment groups were similar, and any effect associated with this bias is unlikely to be significant.

Conclusions

Although this is a single-center EMR review with a relatively small sample size, the data suggest that receipt of IFX or IFX-A is associated with similar responses in the treatment of HS. Given the increasing number of biosimilar drugs becoming available, understanding their safety and effectiveness across indications is vital. Lack of copay and manufacturer assistance programs for off-label use of effective biosimilars is a major limitation to their clinical use. Further data on safety and effectiveness may lead to improved access. Although the initial data are encouraging, further research is warranted to explore the effectiveness and safety of IFX-A in the treatment of HS.