SUMMARY

• The company cannot recommend any practices, procedures or usage that deviate from the approved labeling.
• Prospective, retrospective, and registry-based studies conducted in patients with perianal Crohn’s disease (CD) and perianal fistulizing CD are described below.^1-32

REAL-WORLD DATA ON PATIENTS WITH PERIANAL CD AND PERIANAL FISTULIZING CD

Prospective Study

Bar-Gil Shitrit et al (2020)¹ conducted a prospective, multicenter study to evaluate the efficacy and safety of STELARA for the induction of remission in patients with active CD.

• Of the 106 patients included in the study, 26 had active perianal disease (defined as any actively draining perianal fistula) and 7 had undergone perianal surgery.
• Among patients with active perianal disease at baseline, 77% of patients remained with an active disease at week 8, and 69% of patients at week 24 (P<0.001).

Retrospective Studies

Yao et al (2023)² conducted a retrospective cohort study to evaluate the short-term efficacy of STELARA in patients with perianal fistulizing CD.

Study Design/Methods

• Crohn’s Disease Activity Index (CDAI), perianal CDAI, and Crohn’s anal fistula quality of life (CAF-QoL) were assessed at baseline and at week 16/20.
• Outcomes assessed were as follows:
  • Intestinal clinical remission (CDAI score of <150) and response (reduction of >70 points in CDAI score and/or CDAI score of <150).
  • Fistula clinical remission (absence of any draining fistula) and response (>50% reduction in the number of draining fistulas based on the fistula drainage assessment index).
  • Endoscopic remission (Rutgeerts score ≤i1 or a simple endoscopic score for Crohn’s disease [SES-CD] of ≤2) and response (reduction of 1 grade from baseline in Rutgeerts score or a >50% reduction in SES-CD).
  • C-reactive protein (CRP) normalization (CRP level of <4 mg/L).
  • Radiological fistula healing (the absence of a high-signal track on fat saturated T2 sequences).
    • Improvement was defined as a reduction in the number and volume of fistula and >10% reduction in the magnetic resonance imaging (MRI) signal.
    • No change was defined as the same number of fistulas and volume of inflammation vs baseline.
    • Deterioration was defined as an increase in the size and number of fistula tracks.

Results

• A total of 108 patients were included in the study.
• At week 16/20, intestinal clinical remission and response were achieved in 65.7% and 71.3% of patients, respectively.
• Fistula clinical remission and response were achieved in 40.7% and 63.0% of patients, respectively.
  • Fistula clinical remission/response was achieved in 80.3% vs 43.2% of patients who achieved intestinal clinical remission vs those who did not.
• Among patients who underwent endoscopic re-examination (n=99), endoscopic remission and response were achieved in 31.5% and 45.4% of patients, respectively.
• CRP normalization was achieved in 55.6% of patients.
• Among patients who underwent MRI re-examination (n=67), radiological outcomes of healing, partial response, no change, and deterioration were achieved in 44.8%, 31.4%, 13.4%, and 10.4% of patients, respectively.
• The amelioration in fistula radiological outcomes was confirmed by the significant reduction in the Van Assche score from 9 (interquartile range [IQR], 7.0-14.0) at baseline to 5.5 (IQR, 0.0-10.0) after STELARA treatment (P<0.001).
• Rate of intestinal clinical remission was significantly higher in patients who were anti-TNF naïve vs those who were anti-TNF exposed (78.9% vs 58.6%; P=0.033). There was no significant difference in intestinal clinical response and fistula, endoscopic, and radiological evaluations in anti-TNF naïve vs anti-TNF exposed patients.

Bermejo et al (2022)³ conducted a retrospective, observational, multicenter study within Grupo Español de Trabajo de Crohn y Colitis Ulcerosa (GETECCU; the Spanish Working Group on CD and Ulcerative Colitis) to evaluate the short-term efficacy and safety of intravenous (IV) reinduction with STELARA in patients with CD who had lost response to STELARA.

• Of the 53 patients included in the study, 22 (41.5%) had perianal disease at baseline.
• Clinical response was defined as a decrease of ≥3 points in Harvey-Bradshaw Index (HBI) score from the baseline.
• Clinical remission was defined as a final HBI score of ≤4 points.
• By week 16, 4 (50%) patients with active perianal disease responded with cessation of drainage. Among those who had not responded by week 16, there was no improvement.
• In multivariable analysis, based on absence of perianal disease, the odds ratio (OR) at week 16 for those who achieved remission vs those who did not was 5.2 (95% confidence interval [CI], 1.1-24.8; P=0.037).
  • For patients who responded vs those who did not, the OR was 6.2 (95% CI, 1.6-23; P=0.007).

Casanova et al (2022)⁴ conducted a retrospective, multicenter study to evaluate drug persistence, effectiveness, and safety of STELARA and vedolizumab in the treatment of complex perianal fistula in patients with CD (HEAL Study). Results specific to patients treated with STELARA are reported below.

Study Design/Methods

• Patients who initiated treatment with STELARA or vedolizumab ≥6 months before study enrollment were included.
• Clinical remission was defined as no drainage through the fistula upon gentle pressure (per Fistula Drainage Assessment Index) based on physician’s assessment.

Results

• There were 136 patients receiving STELARA with a median follow-up duration of 27 months (IQR, 15-38).
• During follow-up, 24 (19%) patients discontinued STELARA. The incidence rate of STELARA discontinuation (per patient-year [PY]) was 8% (95% CI, 5-11).
• The rate of persistence of STELARA at 1 and 2 years was 89% and 82%, respectively.
• Clinical remission was achieved in 54% of patients with a median time to clinical remission of 6 months (IQR, 4-9).
  • Among these patients, 27% relapsed during follow-up. The relapse rate (per PY) was 11% (95% CI, 7-17).
  • The probability of relapse at 1 and 2 years was 10% and 25%, respectively.
  • In the multivariable analysis, no variable was associated with the likelihood of discontinuation or the risk of relapse.
• Adverse events (AEs; most of them mild) were reported in 6% of patients treated with STELARA.

Gubatan et al (2022)⁵ conducted a retrospective cohort analysis in patients with perianal CD who were exposed to treatment with anti-TNF agents, STELARA, or vedolizumab at the time of perianal disease diagnosis.

Study Design/Methods

• Of the 311 patients included in the study, 16 (5.2%) received STELARA at the time of perianal disease diagnosis.

Results

• Compared with no biologic use, STELARA use was associated with increased rates of perianal fistula closure (hazard ratio [HR], 3.58; 95% CI, 1.0412.35; P<0.05) and decreased rates of perianal abscess recurrence (HR, 0.20; 95% CI, 0.07-0.56; P<0.01) at 5 years.
• Compared with no biologic use, STELARA use was not associated with rates of surgical intervention (P=0.31), colectomy (P=0.50), or permanent diversion (P=0.17).
  • In patients who switched to another anti-TNF agent, there were no differences in the rates of perianal fistula closure (P=0.58) or perianal abscess recurrence (P=0.87) compared with those who received STELARA after the first antiTNF failure.
• Switching to vedolizumab (n=8) after the first anti-TNF failure was associated with decreased rates of perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96; P<0.05) compared with switching to STELARA (n=17).
• There were no significant differences in the rates of surgical intervention, colectomy, permanent diversion, or perianal abscess recurrence among patients who switched to vedolizumab vs STELARA after the first anti-TNF failure.

Matsumoto et al (2022)⁶ conducted a prospective, multicenter, observational, postmarketing surveillance study in Japan to evaluate the effectiveness and safety of STELARA through 52 weeks for the treatment of perianal manifestations of CD.

Study Design/Methods

• Patients with moderately to severely active CD with a history of failure or intolerance to previous treatment from medical facilities were included.

Results

• Among the 341 patients enrolled in the study, 197 and 229 were included in the efficacy and safety analysis sets, respectively.
• Clinical remission rates among patients with (n=60) vs without (n=137) baseline perianal disease were not significantly different (68.3% vs 59.9%).
• Similar improvement in CDAI scores from baseline through week 52 was observed between patients with and without perianal disease.
• Common adverse drug reactions (ADRs) occurring in >0.5% of patients were worsening of CD, anal abscess, upper respiratory tract inflammation, pyrexia, influenza, and intestinal obstruction. No new safety signals were identified.

Newman et al (2022)⁷ conducted a retrospective study to evaluate the responses to STELARA and vedolizumab in patients with fistulizing CD.

• Of the 68 patients included in the study, 37 had perianal fistulas (26 patients receiving STELARA and 11 patients receiving vedolizumab).
• In unadjusted analyses, among patients who were on therapy for >1 year and did not have surgical fistula repair, 79% and 100% of patients in the STELARA and vedolizumab groups, respectively, still had an active fistula at 1 year (P=0.30).
• There was no significant difference between vedolizumab and STELARA in the development of new fistulas (multi-state model P=0.28) or management of surgical CD (multi-state model P=0.70).
• According to adjusted multistate modeling, vedolizumab was significantly more likely to be discontinued compared with STELARA (P<0.0001), mostly due to inadequate overall clinical response.

Attauabi et al (2021)⁸ conducted a multicenter cohort study to evaluate the clinical remission and response of STELARA in patients with active perianal fistulas.

Study design/Methods

• Of the 18 patients with active fistulizing CD included in the study, 10 had complex fistulas with 2 openings.
• Fistula response was defined as a combination of the physician’s objective assessment and the patient’s self-reported improvement in disease symptoms without the need for surgical procedures compared to baseline.
• Fistula remission was defined as healing with no secretion or symptomatic activity.

Results

• For the proportion of patients with perianal CD who achieved fistula response through week 52, see Table: Proportion of Patients with Perianal CD Experiencing Fistula Response.

• No patients experienced clinical remission through week 24, and the data at week 52 could not be determined accurately.
• One patient discontinued STELARA at week 8 due to primary nonresponse.
• No patients reported AEs during the 52 weeks of follow-up.

Bacaksiz et al (2021)⁹ conducted a retrospective study evaluating the 52-week clinical data of patients receiving STELARA for the treatment of moderate to severe CD.

Study Design/Methods

• Of the 10 patients included in the study, 5 had perianal disease.
• Clinical response was defined as a decrease of 70 points in CDAI score and clinical remission was defined as a CDAI score of <150. Additionally, a decrease of ≥3 points in HBI score was accepted as clinical response and an HBI score of ≤4 was accepted as clinical remission.

Results

• For the CDAI and HBI scores through week 52, see Table: CDAI and HBI Scores at Weeks 0, 8, and 52.

• Patient 4 responded to induction therapy and achieved remission; however, STELARA was replaced with anti-TNF therapy for the treatment of ankylosing spondylitis (AS).
• In patients 6 and 10, STELARA was eventually discontinued due to nonresponse and surgery for ileus, respectively.

Crispino et al (2021)¹⁰ conducted an observational, single-center study to evaluate clinical response to STELARA in patients with CD who had perianal lesions refractory to antiTNF therapy.

Study Design/Methods

• Of the 9 patients included in the study, 5 and 4 had active perianal fistula and inactive perianal CD, respectively, at STELARA initiation.
• Fistula response was defined as a combination of the physician’s judgment and the patient’s self-reported improvement with no need of unscheduled surgical treatment.
• Fistula remission was defined as healing with no secretion or symptomatic activity.

Results

• For the number of patients with active perianal disease who achieved treatment response through week 52, see Table: Patients with Active Perianal Disease Experiencing Treatment Response.

• In patients with inactive perianal disease, 2 (50.0%) had recurrence of perianal lesions.
• No AE was observed.
• One patient who initially responded had a loss of response after 78 weeks but regained the response after reinduction with IV STELARA.

Fumery et al (2021)¹¹ conducted a retrospective, multicenter study to evaluate the effectiveness and safety of dose intensification of STELARA from 90 mg every 8 weeks (q8w) to every 4 weeks (q4w) in patients with CD who had incomplete or loss of response to STELARA.

• Of the 100 patients included in the study, 47 had perianal CD at baseline.
• Sixteen patients underwent dose intensification with STELARA for perianal disease and 7 for both perianal and luminal CD.
  • Among these patients, 14 (61%) showed an immediate response according to physician judgement, 5 (22%) had closure of perianal fistula at the end of follow-up, and 4 experienced worsening perianal CD requiring perianal surgery during follow-up.

Godoy Brewer et al (2021)¹² conducted a retrospective, single-center cohort study to evaluate the efficacy of STELARA in the treatment of perianal CD.

Study Design/Methods

• Thirty-one patients with CD and active perianal disease were included, of whom 27 had 6-month and 9 had 12-month follow-up data.
• Provider-based perianal fistula response was defined as at least 50% decrease in fistula drainage compared with baseline as assessed by the provider’s physical examination without need for surgical intervention’.
• Provider-based perianal fistula remission was defined as closure of the external fistula opening and complete cessation of drainage with compression of the tract.
• Patient-reported symptomatic response was defined as patient-reported improvement in fistula pain and/or decreased drainage.
• Patient-reported symptomatic remission was defined as patient-reported absence of perianal pain and complete cessation of fistula drainage.

Results

• For the number of patients who achieved treatment outcomes, see Table: Patients Achieving Provider-Based and Patient-Reported Outcomes at 6 and 12 Months

• At 6-month follow-up, 1 patient had worsening perianal disease.
• Overall, 8 (29.6%) patients required dose escalation within 6 months of STELARA induction, of whom 4 (50%) experienced perianal symptomatic improvement.
• Among the 25 patients with inactive perianal disease at the time of STELARA induction, during the mean follow-up time of 86.2 ± 49 weeks, 1 patient developed a novel perianal abscess requiring drainage 1 year after the induction of STELARA.
  • No other patient developed a flare of the perianal disease.
• Overall, 6 patients developed infections, 2 developed infusion/injection site reactions, and 6 developed other AEs.

Kamperidis et al (2021)¹³ conducted a retrospective, observational, multicenter study to evaluate the effect of STELARA in patients with moderate to severe CD.

• Of the 134 patients included in the study, 49 (36.6%) had perianal disease and 19 (14.2%) had perianal fistulating disease.
• According to the univariate analysis conducted at the last follow up, 4 (20%) patients who discontinued STELARA and 16 (80%) patients who continued STELARA required dose escalation.
• Data on the outcomes were available in 16 of 19 patients with perianal fistulating disease.
  • Thirteen patients had no evidence of fistula response (improvement or closure of fistula on examination, removal of seton or radiological improvement on pelvic MRI) and 3 demonstrated a response on examination or imaging.

Kartikeya et al (2021)¹⁴ conducted a retrospective study to evaluate the efficacy of STELARA in patients with CD who had previously received anti-TNF therapy.

• Of the 34 patients included in the study, 50% had fistulizing disease.
• Among patients with fistulizing disease, 70% achieved clinical remission with STELARA.

Manlay et al (2021)¹⁵ conducted a retrospective study to compare the short- and long-term effectiveness of STELARA and vedolizumab in patients with CD who were refractory to anti-TNF therapy.

Study Design/Methods

• Of the 312 patients included in the study, 56 had concomitant active fistulizing perianal lesions at baseline (STELARA, n=39 and vedolizumab, n=17).
• Active perianal lesions included persistence of draining, perianal pain, or abscesses.

Results

• For the rates of active and novel active perianal lesions at weeks 14, 24, and 54, see Table: Rates of Active and Novel Active Perianal Lesions

Ollech et al (2021)¹⁶ conducted a retrospective study to determine the effectiveness of STELARA dose interval shortening in patients with CD who were not responding to STELARA 90 mg subcutaneously (SC) q8w and were dose escalated to STELARA 90 mg SC q4w.

• Of the 110 patients included in the study, 11 had active perianal disease at the time of the STELARA dose escalation.
• Among 11 patients with active perianal disease, 5 reported resolution of perianal disease (HBI ≤4) within 6 months of dose escalation.
• The HR for presence of perianal disease vs inflammatory behavior (Montreal classification) by univariate analysis was 1.26 (95% CI, 0.68-2.34) for clinical remission, 0.97 (95% CI, 0.49-1.95) for biologic remission (CRP normalization), and 1.56 (95% CI, 0.64-3.80) for endoscopic remission.

Plevris et al (2021)¹⁷ conducted a retrospective, multicenter, cohort analysis study to evaluate the real-world efficacy and safety of STELARA in patients with CD.

Study Design/Methods

• Of the 216 patients included in the study, 37 (17.1%) had active perianal disease (defined by MRI) at STELARA initiation.
• Perianal response was determined by reduction in enhancement, closure, or fibrosis of tract as observed on follow-up MRI vs baseline MRI.

Results

• Among patients with active perianal disease, the cumulative perianal fistula response rate was 12.5% at 6 months and 53.1% at 12 months.
• Surgical procedures for perianal disease were performed in 13 patients, including fistulotomy in 1 patient and examination under anesthesia with drainage of the abscess and seton insertion in 12 patients.
• The HR for primary loss of response by univariable analyses for patients with perianal disease was 0.37 (95% CI, 0.09-1.60; P=0.18).
• A patient >60 years old, with a history of complex CD with multiple operations for severe penetrating and perianal disease, died while receiving STELARA. The patient received 2 doses of STELARA as a last attempt to control disease as he was not a further surgical candidate. Following the first SC dose of STELARA, he developed intra-abdominal/perianal sepsis, which did not respond to therapy.

Richard et al (2021)¹⁸ conducted a retrospective, single-center study to report the MRI follow-up in patients with active perianal fistulizing CD refractory to anti-TNF therapy treated with STELARA.

• Twenty patients were included in the study.
• After a mean treatment duration (standard deviation [SD]) of 17.6 (12.3) months, significant changes in CRP, Van Assche index, and Magnetic Resonance Novel Index for Fistula Imaging in Crohn’s Disease (MAGNIFI-CD) compared to baseline were observed; see Table: CRP Levels, Van Assche Index Scores, and MAGNIFI-CD Scores at Baseline and After Second MRI.

Chapuis-Biron et al (2020)¹⁹ conducted a retrospective, multicenter, observational study (BioLAP) in centers affiliated with Groupe d’Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) to evaluate the effectiveness of STELARA and identify the predictors of successful treatment (clinical success assessed by the investigator at 6 months of therapy and no medical/surgical intervention on perianal disease) in patients with perianal CD.

• Of the 207 patients included in the study, 148 and 59 had active and inactive perianal disease, respectively, at STELARA initiation.
• Treatment success was achieved in 57 (38.5%) patients with active perianal disease.
• In patients with inactive perianal CD at initiation, 13/59 patients had recurrence of perianal disease, 12/13 had secondary lesions, and 8/59 required perianal disease treatment while on STELARA.
• Treatment-related AE was observed in 2/56 patients which required drug discontinuation, and 1 malignancy was reported.

Glass et al (2020)²⁰ conducted a retrospective, single-center cohort study to evaluate the effectiveness and safety of STELARA dose escalation in both luminal and perianal CD.

• Of the 38 patients included in the study, 24 (63%) had perianal disease.
• Improvement in perianal disease was defined as a composite outcome of 1 or more of the following- steroid-free clinical response, objective improvement in disease on follow up computed tomography (CT), MRI or endoscopy, or normalization of CRP- reflecting disease response as documented by the treating physician.
• Among 24 patients with active perianal disease, 12 (50%) patients showed evidence of improvementafter dose escalation.

Harris et al (2020)²¹ conducted a retrospective, observational cohort study to evaluate the effectiveness of STELARA in patients with CD.

• Of the 84 patients included in the study, 53 had penetrating or perianal disease and 8 had active perianal disease at baseline.
• Among 8 patients with active perianal disease at baseline, 3 had a documented response(improvement in Physician’s Global Assessment [PGA] category) at postinduction review, 2 were defunctioned, and 3 had an ongoing disease.

Satyam et al (2018)²² conducted a retrospective chart review to evaluate the efficacy of STELARA in patients with perianal CD.

• Of the 44 patients included in the study, 21 had perianal disease.
• Perianal response was defined as an improvement in perianal symptoms as assessed by the treating physician and continuation of STELARA.
• Perianal remission was defined as the complete absence of perianal symptoms based on history, physical exam, and endoscopy, if performed.
• Perianal response was observed in 7 (33%) patients, of whom 6 had been on STELARA for >1 year.
• Perianal remission was observed in 2 (9.5%) patients.
• STELARA was discontinued in 3 patients due to headache, insurance issues, and nonresponse with continued severe disease on endoscopy.

Wils et al (2018)²³ conducted a retrospective, observational, multicenter cohort study to evaluate the longterm efficacy and safety of STELARA and identify the predictive factors of STELARA failure-free persistence in patients with CD who were refractory to anti-TNF therapy.

• Of the 88 patients included in the study, 9 had perianal disease at STELARA initiation.
• Overall, 6 patients with perianal disease achieved clinical remission during follow-up.
  • After 12, 25, and 30 months of follow-up, 1 patient discontinued STELARA due to personal reasons, 1 due to pregnancy, and 1 due to a serious adverse event (SAE) (development of an anal adenocarcinoma).
  • Three patients discontinued STELARA due to loss of response at 6, 24, and 26 months, respectively.
  • One patient underwent surgery during follow-up for perianal drainage.

Battat et al (2017)²⁴ conducted a study to evaluate the efficacy of STELARA in patients with perianal fistulizing CD.

• Of the 62 patients included in the study, 17 had a history of perianal fistulizing disease and 6 had actively draining fistulas prior to STELARA initiation.
• At ≥6 months, 4 of 6 patients had a >50% reduction from baseline in the number of draining fistulas, and 2 of 6 patients had closure of all fistulas.
• At ≥6 months, of the 6 patients who had active fistulas, 3 attained clinical response and 2 attained clinical remission (HBI<5), 2 achieved steroid-free clinical remission, 3 attained endoscopic response, and 2 attained endoscopic remission.

Ma et al (2017)²⁵ conducted a retrospective, multicenter, observational cohort study to evaluate the clinical, endoscopic, and radiographic responses and remission outcomes in patients with refractory CD who were receiving STELARA.

• Of the 167 patients included in the study, 45 (26.9%) had perianal disease at STELARA initiation.
• Among the patients with perianal disease, 14 (31.1%) achieved complete healing, as demonstrated by pelvic MRI or dedicated pelvic contrastenhanced ultrasound.

Tsistrakis et al (2017)²⁶ conducted a retrospective chart review to evaluate the efficacy of STELARA in patients with fistulizing CD.

• The study included 9 patients with perianal and/or rectovaginal fistulas.
• Fistula response was defined as decrease in fistulous drainage or partial healing of fistulas.
• Fistula healing was defined as complete closure of fistulas.
• Fistula healing, fistula response, and no response were observed in 1, 4, and 2 patients, respectively.

Khorrami et al (2016)²⁷ conducted a retrospective, observational, open-label study to evaluate the effectiveness and safety of STELARA in patients with refractory CD.

• Of the 116 patients included in the study, 58 (50%) had perianal disease, and 18 had active perianal disease at STELARA initiation.
• Perianal disease improved (based on physician judgment) in 11 of 18 (61%) patients with perianal fistulas.
• New perianal abscesses were reported in 2 patients during the treatment with STELARA.
• In the univariate analysis, perianal disease was not considered to be a predictive factor for the initial (OR, 1.98; 95% CI, 0.72-5.46; P=0.18) or long-term (OR, 1.77; 95% CI, 0.84-3.74; P=0.13) response with STELARA.

Kopylov et al (2014)²⁸ conducted a retrospective, observational, open-label study to evaluate the use of STELARA in patients with CD who were refractory to anti-TNF therapy.

• Of the 40 patients included in the study, 13 (35.3%) had perianal disease.
• In patients with perianal disease, an initial response (as assessed by the treating physician) was achieved in 9 (69.2%) patients.
• Overall, 4 patients with an initial response reached 12 months of follow-up, of whom 3 sustained their clinical response.

Registries

Barreiro-de Acosta et al (2023)²⁹ conducted a retrospective study to evaluate the effectiveness of biologic agents, including STELARA, in patients with CD complicated with internal fistulizing disease, from the Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales (ENEIDA) registry. Summarized below are data pertinent to STELARA.

Study Design/Methods

• The primary endpoint was surgical procedures performed for intra-abdominal penetrating complications during follow-up.
• Secondary outcomes included the development of a new abdominal abscess, need for percutaneous drainage, change in the number of fistulous tracts, and the proportion of patients with fistula healing.
• Fistula closure was defined as closure of the fistulous tract as evident on cross-sectional imaging.

Results

• Of the 760 patients included in the study, 69 were receiving STELARA.
• At baseline, among patients who received STELARA, the median number of fistulas was 1 (IQR, 1-3).
• For outcomes observed during follow-up in each treatment group, see Table: Primary and Secondary Outcomes in Each Treatment Group.

• The cumulative probability of remaining free of surgery at 1, 3, and 5 years of follow-up, respectively, was 81%, 72%, and 67% for anti-TNF agents; 82%, 70%, and 70% for STELARA; and 73%, 64%, and 64% for vedolizumab.
• There were no differences in the risk of surgery between the adalimumab, infliximab, STELARA, and vedolizumab groups at a median duration of 13, 7, 5, and 6 months, respectively, over time (HR, 1.06; 95% CI, 0.43-2.61; P=0.89 for STELARA; HR, 1.13; 95% CI, 0.14-9.29; P=0.91 for vedolizumab).
• Among the patients treated with STELARA, there were no factors associated with a risk of surgery.
• The median duration of drug persistence for anti-TNF agents, STELARA, and vedolizumab was 15 months (IQR, 4-36), 3 months (IQR, 2.5-6.3; HR, 1.83; 95% CI, 1.07-3.13; P=0.03), and 11.5 months (IQR, 2-27; HR, 1.99; 95% CI, 0.82-4.83; P=0.13), respectively.
• Patients in the anti-TNF group required subsequent therapy with another anti-TNF agent (80%), STELARA (15%), or vedolizumab (5%) following drug withdrawal. All patients in the STELARA and vedolizumab groups requiring subsequent therapies received anti-TNF agents.
• No AEs were reported with STELARA treatment.

Straatmijer et al (2021)³⁰ conducted a prospective study of patients enrolled in the Initiative on Crohn and Colitis (ICC) registry to evaluate the 2year effectiveness and safety of STELARA in patients with CD.

Study Design/Methods

• Of the 252 patients included in the study, 33 (13.1%) had perianal disease and 29 (11.5%) had ≥1 active fistulas.

Results

• Eighteen (62.1%) patients had spontaneous drainage of fistulas, and 11 (37.9%) patients had fistula drainage after gentle manual pressure.
• Fistula remission was observed in 5 (17.2%), 11 (37.9%), 11 (37.9%), and 6 (20.7%) patients after 12, 24, 52, and 104 weeks of treatment, respectively.
• Six of these patients underwent perianal surgery during follow-up. In 2 of these patients, surgery occurred after 52 weeks while in clinical remission.
• Seven patients developed new perianal fistulas during follow-up, of whom 5 developed fistulas within 24 weeks of treatment initiation.
• Five of these patients achieved fistula remission within 2 years of follow-up and 1 patient developed perianal fistula after 52 weeks of therapy while in steroid-free remission.
• Four patients had perianal abscesses at baseline which were absent at week 12.

Iborra et al (2020)³¹ conducted a retrospective, multicenter study to evaluate the long-term effectiveness of STELARA in patients with refractory CD from the ENEIDA registry.

• Of the 407 patients included in the study, 126 (31%) had perianal involvement.
• A total of 33 (8%) patients experienced exacerbation of perianal disease (25 with a history of perianal disease and 8 with de novo disease).
  • Treatment was discontinued in 15 patients, and 3 patients underwent perianal surgery during follow-up.
• During the 1-year follow-up, 53 patients required surgery, 3 due to perianal disease.

Noa et al (2018)³² described the rates of perianal improvement in patients who received STELARA. Patients with perianal fistulas at STELARA initiation were evaluated for improvement at the 6-month follow-up based on standard clinical assessment (cessation of drainage and no abscess).

• Of the 74 patients included in the study, 29 (39%) had perianal disease.
• Overall, 10 of 16 (62.5%) patients with active perianal fistulas at baseline showed improvement by the 6month follow-up.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 22 March 2024.