Summary

• The company cannot recommend any practices, procedures or usage that deviate from the approved labeling.
• Specific studies have not been conducted in patients with renal insufficiency.¹
• Summaries of retrospective studies and case reports published in the literature are described below.^2-12

Company core data sheet

• Specific studies have not been conducted in patients with renal insufficiency.¹

CLINICAL DATA

Retrospective Studies

Maghfour et al (2020)² reported the results from a retrospective study of patients treated with a biologic agent for moderate to severe plaque psoriasis (PsO) and coexisting chronic kidney disease (CKD) prior to biologic drug initiation.

• The analysis consisted of PsO patients who were treated at Tulane Medical Center from 2011 to 2019.
• The cohort included patients who were treated with adalimumab, infliximab, ixekizumab, secukinumab and STELARA.
• Statistical analysis was conducted on the collective group of identified patients, and not analyzed by individual biologic agent.
• Included in the study were any patients categorized as having CKD (defined as an estimated glomerular filtration rate (eGFR) persistently lower than 60 mL/min/1.73 m² for 3 months).
• Patients were excluded if they had received more than 1 biologic drug prior to study initiation.
• Thirty-four of the 533 patients reviewed met the inclusion criteria of which 32 were biologic naive and 2 (5.9%) were excluded after switching biologic drugs during the study period.
• Data from STELARA treated patients are summarized in Table: Characteristics of PsO Patients on STELARA Treatment with CKD.
  • At baseline the overall mean age was 63.5 years.
  • Biologic average duration of use was 2.3 years. All STELARA treated patients had concomitant hypertension while 57.0% (4/7) of patients had diabetes.
  • The overall mean eGFR after biologic treatment compared to baseline was 54.2 mL/min/1.73 m² per year and 53.2 mL/min/1.73 m² per year, respectively.
  • Only 1 patient initiated on STELARA saw an improved eGFR over time (an eGFR increase from 51 to 57 mL/min/1.73 m²).

Larquey et al (2017)³ conducted a retrospective multicenter study to analyze the data of 5 patients with severe PsO treated with biologics who were receiving hemodialysis for CKD, without psoriatic arthritis.

• One patient was treated with STELARA, 3 with etanercept, and 1 with infliximab.
• The treatment was effective in 5 cases, even under hemodialysis, with Psoriasis Area and Severity Index (PASI) 75 or PASI 100.
• Measurement of serum concentrations of the molecules used were carried out by Theradiag (LISATRAKER box; ELISA method).
• The median half-life of STELARA is approximately 3 weeks.
• For patient 1, plasmatic ustekinumab concentration decreased gradually with repetition of dialysis sessions between 2 injections; the concentration was decreased 2-fold at 5 weeks and became undetectable at 10 weeks. Antiustekinumab antibodies were negative.

Case Reports

Spathakis et al (2023)⁴ reported a case of a patient undergoing hemodialysis for end stage renal disease and treated with STELARA for treatment-refractory Crohn’s disease (CD).

• A 45-year-old female patient with a 22-year history of refractory, fistulizing CD presented with intestinal perforation.
• Prior to developing intestinal perforation, the patient experienced several complications related to CD, including perianal fistulas, enterocutaneous fistula, descending colon stricture, and enteropathic arthritis. The patient received treatments for CD, including mesalazine, adalimumab, and infliximab, however, the patient did not achieve disease remission.
• The patient also has a history of CKD and was hospitalized 3 times due to muscle weakness/paralysis caused by severe hypokalemia and 1 time for a urinary tract infection. Patient was initiated on thrice-weekly hemodiafiltration (HDF) sessions due to progressively worsening renal function and electrolyte imbalances.
• The patient’s laboratory tests at the time of presentation revealed the following:
  • Mild macrocytic anemia and anisocytosis (hemoglobin [Hb], 10.7 g/dL; hematocrit [HCT], 32.4%; red blood cells [RBCs], 3.24x10⁶/µL; mean corpuscular volume [MCV], 100 fl; red cell distribution width-standard deviation [RDW-SD], 74%)
  • Renal insufficiency (urea, 46 mg/dL; creatinine [Cr], 3.9 mg/dL)
  • Liver dysfunction (aspartate aminotransferase [AST], 75 mg/dL; alanine aminotransferase [ALT], 94 mg/dL; lactate dehydrogenase [LDH], 316 mg/dL)
  • Elevated fecal calprotectin levels (566.9 µg/g)
• STELARA was initiated at an induction dose of 260 mg intravenously (IV; body weight, 50 kg) followed by a maintenance dose of 90 mg subcutaneously (SC) once every 2 months, administered within 24 hours of the last HDF session.
• The patient achieved clinical remission of CD with minimal symptomatology (fecal calprotectin, 7.5 µg/g; Harvey Bradshaw Index, 2) while concomitantly receiving an SC dose of STELARA with no reported adverse events.
• The patient continues to undergo HDF sessions for CKD, with Cr levels remaining high but stable at 3.4 mg/dL, while blood urea levels have gradually been improving, leading to a decrease in session frequency.

Michelerio et al (2021)⁵ reported a case of a patient undergoing hemodialysis for end stage renal disease and treated with STELARA for severe PsO.

• A 48-year-old male patient with a 25-year history of severe PsO and 10-year history of CKD (stage G3b A3) secondary to focal segmental glomerulosclerosis started hemodialysis due to worsening kidney function.
• The patient’s PsO was no longer controlled with past treatments of topicals, photochemotherapy, and systemic treatment which included methotrexate (discontinued due to transient myelosuppression) and adalimumab 40 mg was started (every 2 weeks starting 1 week after initial dose).
• After 2 weeks of starting adalimumab, the patient developed acute water retention and facial edema requiring additional hemodialysis treatments and adalimumab was switched to STELARA 45 mg every 3 months.
• A few days post STELARA treatment, the patient achieved a PASI 75 and almost complete regression of PsO lesions (PASI 90) at 3 months.
• The patient underwent a kidney transplant 7 months later and STELARA treatment was not discontinued prior to surgery with the last dose administered 1 month prior to transplant. STELARA was discontinued after surgery and the patient’s PsO remained in remission 1 year post-transplant.

Haebich et al (2018)⁶ reported a case of STELARA treatment of ulcerative colitis (UC) associated pyoderma gangrenosum in a patient with adalimumab-induced renal failure.

• A 54-year-old woman with UC treated by pancolectomy 20 years ago presented with painful debilitating bilateral lower limb pyoderma gangrenosum (PG) of 6 years duration, confirmed by repeated histology. The largest ulcer was 10 x 15 cm.
• No improvement was observed with topicals (corticosteroids or tacrolimus), oral prednisolone (1 mg/kg per day), tetracycline antibiotics, ciclosporin (5 mg/kg daily), mycophenolate, dapsone, methotrexate alone nor potassium iodide.
• Initial response followed by resistance was observed with infliximab, despite combination with methotrexate, over a period of 18 months and the patient was switched to adalimumab, which resulted in increased ulcer pain and acute renal failure (serum creatinine [sCr], rise from 127 to 512 mmol/L).
• Adalimumab-induced acute glomerular nephritis was diagnosed.
  • The adalimumab was stopped and together with the use of high-dose oral prednisolone (1 mg/kg per day) resulted in improved renal function.
• STELARA was initiated in 2017. The PG pain subsided after the first injection and after 3 treatments the ulcers halved in area and 1 leg ulcer has healed, enabling reduction in the oral prednisolone dose while maintaining stable renal function.

Nimmannitya et al (2016)⁷ reported the use of STELARA in a male patient with end stage renal disease on hemodialysis.

• The patient was a 57-year-old male with a 30-year history of refractory plaque PsO which was partially controlled by topical treatments and ultraviolet therapy.
• Patient has a 6 year history of hemodialysis for chronic renal failure due to polycystic kidney disease.
• Patient’s PsO involved the scalp, trunk, upper and lower extremities. There was no joint involvement. PASI score and Physician Global Assessment (PGA) were 15.4 and 3.0, respectively at presentation and Cr was 13.1 mg/dL.
• The first 2 STELARA 45 mg doses were administered 4 weeks apart and the PASI score decreased to 9.1 at week 4, 2.2 at week 8, and 1.3 at week 12.
• PASI 90 was achieved after the second dose and STELARA was continued every 12 weeks. One year after starting STELARA, lesions worsened and the PASI score and PGA were 7.5 and 2.0, respectively.
• STELARA dose was increased to 90 mg and the PASI score decreased to 2.8 after the first injection and remained well-controlled. Renal function remained stable throughout treatment duration.

Kluger et al (2015)⁸ reported the use of STELARA in a male patient with immunoglobulin A nephropathy (IgAN).

• The patient was a 56-year-old Caucasian male with a diagnosis of severe PsO and peripheral arthritis who previously received gold therapy, psoralen + ultraviolet A therapy, methotrexate, and etanercept.
• The patient received infliximab 5 mg/kg every 8 weeks. After the fifth infusion, the patient experienced microscopic hematuria and proteinuria (1-2.5 g/24 hours). Creatinemia was 100 µM and glomerular filtration rate (GFR) was 73 mL/min/1.73 m².
• After the seventh infusion, infliximab was stopped due to lack of efficacy in the treatment of PsO. IgAN was diagnosed on kidney biopsy.
• Two months after stopping infliximab therapy, the patient started STELARA 45 mg every 3 months. After 6 and 9 injections of STELARA, proteinuria was 0.3 g/dL and 0.82 g/dL respectively. GFR was 85 mL/min/1.73 m² and 95 mL/min/1.73 m² respectively.
• The patient received 11 injections of STELARA with an overall improvement in skin and joint manifestations.
• STELARA was withdrawn after approximately 2.5 years of therapy. The patient remained symptom-free, with stable renal function despite slight elevation of renal parameters (creatinemia 148 µM, GFR 73 mL/min/1.73 m², proteinuria 1.19 g/day).

Umezawa et al (2015)⁹ reported 3 cases of the use of STELARA in patients with PsO undergoing hemodialysis.

Case 1

• The patient was a 68-year-old male with a 5-year history of PsO and had never had swollen joints. Patient developed chronic renal failure 15 years prior due to diabetes and had been undergoing hemodialysis 3 times a week for 10 years.
• Topical treatments were primarily given with an insufficient response. PASI score was 10.4 and Dermatology Life Quality Index (DLQI) was 13.
• Pertinent laboratory findings were as follows: blood urea nitrogen (BUN), 47.0 mg/dL; sCr, 9.4 mg/dL; potassium (K), 5.0 mEg/L; C-reactive protein (CRP), 0.05 mg/dL.
• STELARA was initiated at 45 mg dose at week 0, week 4 and every 12 weeks thereafter.
• By week 16, the PASI score had decreased to 0, DLQI had decreased to 0 and the patient continued STELARA without adverse events up to week 52. The patient continued hemodialysis treatment on a regular basis.

Case 2

• The patient was a 64-year-old male who developed chronic renal failure 20 years ago and had been undergoing hemodialysis 3 times a week for 10 years.
• After 6 years of hemodialysis, he developed a skin rash and was diagnosed with PsO vulgaris with no evidence of swollen joints. Patient was unsuccessfully treated with topical corticosteroid and vitamin D3.
• PASI score was 12.4 and DLQI was 2 before initiation of STELARA.
• Pertinent laboratory findings were as follows: BUN, 65.0 mg/dL; sCr, 8.6 mg/dL; K, 5.0 mEg/L.
• STELARA was initiated at 45 mg at week 0, week 4, and every 12 weeks thereafter. By week 16, the PASI score had improved to 0 and DLQI to 1, but PsO gradually worsened. The patient was able to continue STELARA without adverse events up to week 52, with subsequent hemodialysis treatment on a regular basis.

Case 3

• The patient was a 57-year-old male with a 20-year history of PsO who had developed chronic renal failure due to diabetes, and hemodialysis was initiated 3 times a week for 1 year.
• Previous insufficient treatments included topical treatments and narrow-band ultraviolet B therapy. PASI score was 17.2 and DLQI was 16 before initiation of STELARA.
• Pertinent laboratory findings were as follows: BUN, 30.0 mg/dL; sCr, 8.6 mg/dL; K, 5.1 mEg/L; and CRP, 1.94 mg/dl.
• STELARA was initiated at 45 mg at weeks 0 and 4 with prophylactic administration of isoniazid for TB. At week 16 (third scheduled injection), the PASI score decreased to 2.0 and DLQI to 1.0, but CRP increased to 5.0 mg/dL.
• Subsequently, the CRP gradually decreased to approximately 2.0 mg/dL with no specific treatments for 8 weeks, and the patient's improved state was maintained so long as STELARA was not administered.
• STELARA treatment then resumed from week 40 due to recurrence of PsO. The patient has continued hemodialysis treatment on a regular basis.

de Unamuno Bustos et al (2014)¹⁰ reported the use of STELARA in a male patient with end stage renal disease on hemodialysis.

• The patient was a 65-year-old male with a severe refractory PsO for 27 years with a medical history of hypertension, ischemic heart disease, and chronic renal failure 4 years ago.
• After several failed PsO treatments with methotrexate, cyclosporine, acitretin, and phototherapy, patient was unsuccessfully switched to etanercept 50 mg/week which was discontinued 7 months later.
• When PASI score was observed to be 15, the patient was switched to STELARA 45 mg SC initially and 4 weeks later, followed by 45 mg every 12 weeks.
• A significant improvement of the PASI score was noted 4 weeks after the STELARA treatment and subsequent improvements were observed throughout therapy.
• Hemodialysis was initiated while the patient was maintained on STELARA treatment and when GFR reached 13.5 mL/min.
• Seventeen months after initiating treatment with STELARA, significant remission has been observed and there have been no reports of relevant changes in renal function.

Larquey et al (2014)¹¹ reported a case of treatment with STELARA in a patient on hemodialysis with severe PsO.

• The patient was a 34-year-old woman, with a history of morbid obesity and hereditary chronic renal insufficiency, was grafted in 2001, and then given immunosuppressive treatments. Patient underwent hemodialysis in 2007 due to 4 graft rejections.
• Patient had presented with extensive severe PsO since 2011 that started on the scalp, then expanded with guttate lesions and widespread thick plaques, auditory canal lesions, and gluteal crease lesions (PASI: 13.6 and body surface area [BSA]: 16%) which was initially treated with a betamethasone calcipotriol gel. Pruritus was invalidating. Patient did not have any psoriatic rheumatism.
• The patient was treated with SC STELARA 90 mg which was repeated 30 days later and then every 12 weeks thereafter.
• First injections were well tolerated, with an improvement after 3 injections. No side effects were observed.
  • Pathological areas shrank and pruritus vanished (PASI: 4.5 and BSA: 5%). Only secondary plaques remained on the patient’s back, with post-inflammatory depigmented lesions.

Buquicchio et al (2013)¹² describe the use of STELARA in 3 male patients with moderate to severe PsO and Berger disease.

• The 3 patients ranged in age from 35-50 years old and could not be treated with traditional systemic therapies because of concomitant Berger disease (confirmed by renal biopsy and histologic examination that revealed the presence of immunoglobulin A deposits mainly in the renal glomerulus).
• Pre-treatment laboratory evaluations revealed proteinuria and slightly higher levels of creatininemia. After 3 months of STELARA treatment, proteinuria persisted but did not exceed the previous values, while creatininemia and Cr clearance overlapped with the previous values.
• PASI 75 was observed after 12 weeks of treatment. STELARA was effective and well tolerated in all 3 patients, while not causing any worsening in their renal function or comorbidity.
• Proteinuria resolved in 1 patient after 3 months of treatment and this result persisted at the 6-and 12-month check-ups.
• In 1 patient normalization of a renal function parameter was observed.
• At the time of this report, all 3 patients continue to respond to treatment and have renal function evaluations every 3 months.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 May 2024.