SB5 is an approved adalimumab biosimilar with equivalent pharmacokinetics and efficacy, and comparable safety and immunogenicity to reference adalimumab demonstrated in randomized controlled clinical trials enrolling patients with rheumatoid arthritis. |
“Real-world” evidence confirms the effectiveness and safety of SB5 for the treatment of immune-mediated inflammatory diseases for which reference adalimumab has been approved. |
In both controlled and “real-world” settings, SB5 was not associated with reduced efficacy/effectiveness or clinical complications in both naïve and switched patients compared to reference adalimumab. |
The quality of SB5 is tightly controlled and consistent over time, and its unique self-injection device is preferred over other autoinjectors by both patients and healthcare professionals. |
Introduction
Proprietary name | Proper name | License type | Applicant | FDA approval date |
---|---|---|---|---|
Abrilada | Adalimumab-afzb | Biosimilar | Pfizer Inc | Nov 15, 2019 |
Amjevita | Adalimumab-atto | Biosimilar | Amgen Inc | Sep 23, 2016 |
Cyltezo | Adalimumab-adbm | Interchangeable | Boehringer Ingelheim Pharmaceuticals, Inc | Aug 25, 2017 |
Hadlima | Adalimumab-bwwd | Biosimilar | Samsung Bioepis Co., Ltd | Jul 23, 2019 |
Hulio | Adalimumab-fkjp | Biosimilar | Mylan Pharmaceuticals Inc | Jul 06, 2020 |
Hyrimoz | Adalimumab-adaz | Biosimilar | Sandoz Inc | Oct 30, 2018 |
Idacio | Adalimumab-aacf | Biosimilar | Fresenius Kabi USA, LLC | Dec 13, 2022 |
Yuflyma | Adalimumab-atty | Biosimilar | Celltrion Inc | May 23, 2023 |
Yusimry | Adalimumab-aqvh | Biosimilar | Coherus BioSciences, Inc | Dec 17, 2021 |
Indications and usage |
HADLIMA is a tumor necrosis factor (TNF) blocker indicated for Rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (Ps) |
Dosage (administered by subcutaneous injection) |
Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis |
Adults: 40 mg every other week |
Juvenile idiopathic arthritis in pediatric patients ≥ 2 years of age |
10 to < 15 kg (22 to < 33 lbs)—10 mg every other week; 15 to < 30 kg (33 to < 66 lbs)—20 mg every other week; ≥ 30 kg (≥ 66 lbs)—40 mg every other week |
Crohn’s disease |
Adults: 160 mg on day 1; 80 mg on day 15; and 40 mg every other week starting on day 29 |
Pediatric patients 6 years of age and older: 17 to < 40 kg (37 to < 88 lbs)—80 mg on day 1, 40 mg on day 15, 20 mg every other week starting on day 29; ≥ 40 kg (≥ 88 lbs)—160 mg on day 1, 80 mg on day 15, 40 mg every other week starting on day 29 |
Ulcerative colitis |
Adults: 160 mg on day 1, 80 mg on day 15 and 40 mg every other week starting on day 29 |
Plaque psoriasis |
Adults: 80 mg initial dose, followed by 40 mg every other week starting 1 week after initial dose |
Dosage forms and strengths |
Injection |
Single-dose prefilled autoinjector (HADLIMA PushTouch): 40 mg/0.8 mL |
Single-dose prefilled glass syringe: 40 mg/0.8 mL |
Single-dose glass vial for institutional use only: 40 mg/0.8 mL |
Single-dose prefilled autoinjector (HADLIMA PushTouch): 40 mg/0.4 mL |
Single-dose prefilled glass syringe: 40 mg/0.4 mL |
Contraindications |
None |
Warnings and precautions |
Serious infections: Do not start HADLIMA during an active infection. If an infection develops, monitor carefully, and stop HADLIMA if infection becomes serious: Invasive fungal infections, malignancies, anaphylaxis or serious hypersensitivity reactions, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, lupus-like syndrome |
Adverse reactions |
Most common adverse reactions (> 10%): infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash |
Drug interactions |
Abatacept: Increased risk of serious infection |
Anakinra: Increased risk of serious infection |
Live vaccines: Avoid use with HADLIMA |
Stepwise Approach to Build the “Totality of the Evidence” Demonstrating Biosimilarity
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A randomized, single-blind, three-arm, parallel group, single-dose, PK, clinical equivalence study using the SB5-LC formulation conducted in healthy subjects. In this study, a total of 189 subjects were randomized to either receive SB5, EU-sourced adalimumab (EU-ADL), or USA-sourced adalimumab (US-ADL). Each group featured 63 subjects [15].
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A randomized, double-blind, multinational, 52-week, pivotal, comparative efficacy study using the SB5-LC formulation conducted in patients with moderate to severe RA [12, 13]. A total of 542 patients were initially randomized to SB5 (N = 269) or ADL (N = 273). After 24 weeks, the patients in the ADL group were re-randomized to either continue ADL (N = 129; ADL/ADL) or switch to SB5 (N = 125, ADL/SB5).
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A randomized, single-blind, two-arm, parallel-group, single-dose, PK, clinical equivalence study in healthy male subjects comparing the SB5-LC and SB5-HC formulations. A total of 188 healthy subjects were randomized (94 subjects in each group) [20].
Pharmacokinetics
Safety
Efficacy
Immunogenicity
Real-World Evidence
Reference | Study design and data source | Objective | Patient numbers and indication | Follow-up and treatment persistence | Effectiveness outcomes | Safety outcomes |
---|---|---|---|---|---|---|
Rheumatic diseases | ||||||
Bruni 2021 [21] | Prospective, observational cohort study conducted in patients who switched from ADL to SB5 at third-level rheumatology centers in Tuscany, Italy | Investigate the persistence on treatment with SB5, identify predictors of SB5 therapy interruption, and the types of AEs reported and their prevalence | Total = 172 | Follow-up: up to 18 months | NR | AEs: 65 patients (37.8%) |
PsA = 59 (34.3%), axSpA = 61 (35.5%), RA = 34 (19.8%), JIA = 11 (6.4%), Behçet disease = 5 (2.9%), idiopathic uveitis = 2 (1.2%) | Treatment persistence: 94.7% at 6 months, 85.1% at 12 months | SAE: 1 patient (0.6%) | ||||
Müller-Ladner 2022 [22] | Prospective, retrospective, umbrella design, observational study conducted in patients with immune-mediated inflammatory disease who were enrolled at centers in Belgium, Germany, Ireland, Italy, Spain, and the UK, and followed for 48 weeks after switch from ADL to SB5 | Provide insights into outcomes of the transition from ADL to SB5 outside the randomized, controlled, clinical trial setting | PsA | SAE: 15 patients (3.0%) | ||
PsARC (TJC) mean (95% CI) | ||||||
Baseline: 1.7 [0.7, 2.7] | ||||||
Week 48: 1.9 [0.7, 3.0] | ||||||
PsARC (SJC) mean (95% CI) | ||||||
Baseline: 0.7 [0.4, 1.0] | ||||||
Week 48: 0.7 [0.2, 1.1] | ||||||
axSpA | ||||||
BASDAI mean (95% CI) | ||||||
Total = 496 | Follow-up: 48 weeks | Baseline: 2.58 [2.2, 3.0] | ||||
PsA = 162 (32.7%) | Treatment persistence: 80.0% at 48 weeks | Week 48: 2.65 [2.2, 3.1] | ||||
axSpA = 127 (25.6%) | RA | |||||
RA = 207 (41.7%) | DAS28 mean (95% CI) | |||||
Baseline: 2.3 [2.1, 2.5] | ||||||
Week 48: 2.4 [2.2, 2.6] | ||||||
FFbH mean (95% CI) | ||||||
Baseline: 80.0 [73.5, 86.5] | ||||||
Week 48: 77.1 [70.0, 84.1] | ||||||
Parisi 2022 [23] | Real-life study in patients with clinical diagnosis of RA, PsA, and AS over the observational period (visits: 0, 12, 24, and 36 months) | Evaluate the disease activity trend after multiple switching from ADL to its biosimilars (ABP 501 and SB5 subsequently) in a cohort of patients with inflammatory arthritis | Total = 127 | Follow-up: 3-year | DAS28, DAPSA, and BASDAI remained stable over the 3 years (only reported with figure) | NR |
PsA = 52 (40.9%) | Treatment persistence: 82.1%, 78.7%, and 77.5% in AS, RA, and PsA at year 1 | |||||
AS = 34 (26.8%) | ||||||
RA = 41 (32.3%) | ||||||
Inflammatory bowel diseases | ||||||
Lukas 2020 [24] | Data on clinical and disease characteristics were retrieved from the Czech Registry of IBD Patients on Biological and Innovative Therapy [CREdIT Registry] in patients with IBD who underwent a non-medical switch from ADL to SB5 at the Clinical & Research Center ISCARE and Charles University in Prague | Evaluate the efficacy of switching from ADL to SB5 in patients with IBD | Total = 93 | NR | CD | NR |
CD = 80 (86%) | HBI median (IQR) | |||||
UC = 11 (12%) | Baseline: 2 [0, 5] | |||||
IBD unclassified = 2 (2%) | Week 10: 2 [0, 5] | |||||
UC | ||||||
Partial Mayo median (IQR) | ||||||
Baseline: 2 [0, 4] | ||||||
Week 10: 1 [0, 2] | ||||||
Tapete 2022 [25] | Prospective, observational cohort study in patients with IBD and need adalimumab treatment from November 2018 to January 2019 were included in the Tuscan Adalimumab Biosimilar rEgisTry (TABLET) | Analyze the effectiveness and safety of SB5 both in patients who were adalimumab-naïve (naïve group) and in those who underwent a nonmedical switch from ADL to SB5 after a follow-up of 12 months (switch group) | Naïve (SB5) = 48 | Follow-up: 12 months | Naïve (SB5) [baseline, 3, 6, 12 months] | Overall (naïve and switch) AEs: 53 patients (36.3%) |
CD = 37 (77%) | Treatment persistence | CRP mean, mg/dL (SD): 1.2 [1.51], 1.15 [1.51], 0.36 [0.37], 0.57 [0.96] | ||||
UC = 11 (23%) | FC mean, mg/kg (SD): 665 [769], 151 [138], 271 [376], 231 [253] | |||||
Switch (ADL to SB5) = 98 | Naïve (SB5): 95.8%, 81.3%, and 66.7% at 3, 6, and 12 months, respectively | Clinical remission: 81.3%, 72.9%, and 60.4% were in clinical remission at 3, 6, and 12 month, respectively | ||||
CD = 78 (80%) | Switch (ADL to SB5): 96.9%, 92.9%, and 81.6% at 3, 6, and 12 months, respectively | Switch (ADL to SB5) [baseline, 3, 6, 12 months] | ||||
UC = 20 (20%) | CRP mean, mg/dL (SD): 0.8 [1.6], 2.0 [3.1], 0.31 [0.36], 0.75 [115] | |||||
FC mean, mg/kg (SD): 212 [218], 129 [206], 134 [197], 84 [115] | ||||||
Clinical remission: 97.9%, 86.7%, and 72.4% were in clinical remission at 3, 6, and 12 months, respectively | ||||||
Derikx 2021 [26]* | Retrospective, observational cohort study in NHS Lothian (Scotland) to investigate the long-term effectiveness and safety of SB5 | Investigate long-term outcomes of SB5 in patients with IBD following a switch from ADL to SB5 (switch group) or after start of SB5 (naïve group) | Naïve (SB5) = 225 | Naïve (SB5) | Switch (ADL to SB5) [baseline, week 26, week 52] | Naïve (SB5) |
CD = 175 (78%) | Median follow-up: 18.3 months | |||||
UC = 37 (16%) | Treatment persistence: 77.8% at week 26 and 60.3% at week 52 | Biochemical remission (CRP): 69.9%, 70.7%, and 70.7% | AEs: 39 patients | |||
IBD unclassified = 13 (6%) | Fecal biomarker remission: 69.6%, 58.3%, and 59.6% | |||||
Switch (ADL to SB5) = 256 | Switch (ADL to SB5) | Clinical remission: 82.1%, 77.5%, and 75.4% | Switch (ADL to SB5) | |||
CD = 228 (89%) | Median follow-up: 13.7 months | AEs: 51 patients | ||||
UC = 23 (9%) | Treatment persistence: 84.6% at week 26 and 70.8% at week 52 | |||||
IBD unclassified = 5 (2%) | ||||||
Psoriasis | ||||||
Loft 2021 [28] | Crossover-cohort design conducted in patients from the Biological Treatment in Danish Dermatology (DERMBIO) registry who switched from ADL to an adalimumab biosimilar (SB5 or GP2017) between November 1, 2018 and May 1, 2019. The comparator cohort included patients treated with ADL with a visit between May 1, 2017 and November 1, 2018 | Assess the outcomes following a mandatory nonmedical switch from ADL to adalimumab biosimilars (SB5, GP2017) in patients with psoriasis | ADL = 378 | Follow-up: 12 months | NR | ADL |
Switch (ADL to SB5 or GP2017) = 348 | Treatment persistence: 95.8%, and 92.1% in ADL patients and 95.7% and 92.0% in switched patients (ADL to SB5 or GP2017) at 6 months and 12 months, respectively | AEs: 18 patients (5%) | ||||
(SB5 = 162; GP2017 = 186) | Switch (ADL to SB5 or GP2017) | |||||
AEs: 29 patients (9%) | ||||||
Killion 2023 [29] | Single-center, retrospective cohort study conducted in patients with moderate to severe psoriasis who had switched from ADL to adalimumab biosimilars from 2018 to 2022 (records and databases from the British Association of Dermatologists, Biologic Immunomodulators Register [BADBIR] and the National High Tech Prescribing Hub) | Describe the clinical experience of switching patients from ADL to adalimumab biosimilars (SB5, ABP501) and that of switching back to ADL for those intolerant to biosimilars | Switch (ADL to SB5 or ABP501) = 100 | Treatment persistence: 81% at week 16 | Maintenance or improvement in baseline | NR |
(SB5 = 79; ABP501 = 21) | PASI: 91% | |||||
DLQI: 90% | ||||||
Girolomoni 2022 [30] | Prospective observational study in patients with psoriasis receiving SB5 between Jun 01, 2019 and Aug 31, 2021. Patients were identified from the British Association of Dermatologists, Biologic Immunomodulators Register (BADBIR) | Analyze 3-year follow-up data of SB5 from BADBIR | Patients with baseline PASI < 10 | NR | ||
Median PASI (IQR) | ||||||
Baseline: 0.9 (1.8) | ||||||
1 year: 0.5 (2.7) | ||||||
Patients with baseline DLQI < 10 | ||||||
Median DLQI (IQR) | ||||||
Baseline: 6.5 (6.0) | ||||||
1 year: 2.0 (4.0) | ||||||
Naïve (SB5) = 1043 | Mean follow-up: 19.3 months | Patients with baseline PASI ≥ 10 | ||||
Switch (ADL to SB5) = 16 | Treatment persistence: 79.7%, 73.5%, and 72.1% at 1, 2, and 3 years | Median PASI (IQR) | ||||
Baseline: 17.3 (9.5) | ||||||
1 year: 2.2 (5.9) | ||||||
Patients with baseline DLQI ≥ 10 | ||||||
Median DLQI (IQR) | ||||||
Baseline: 19.0 (8.0) | ||||||
1 year: 0.0 (4.0) | ||||||
Hidradenitis suppurativa | ||||||
Ricceri 2020 [31] | Retrospective observational study performed in hidradenitis suppurativa adalimumab-naïve patients who started SB5 and in patients who were switched from ADL to SB5 | Evaluate efficacy and safety of SB5 in hidradenitis suppurativa | Naïve (SB5) | Incidence of AEs prior to and after switching did not differ significantly | ||
IHS4 mean (SD) | ||||||
Baseline: 18.5 [11.3] | ||||||
Week 36: 11.2 [5.4] | ||||||
HiSCR (% achieved): 100% | ||||||
DLQI mean (SD) | ||||||
Baseline: 13 [6.2] | ||||||
Naïve (SB5) = 4 | Follow-up: 36 weeks | Week 36: 10.5 [5.2] | ||||
Switch (ADL to SB5) = 7 | No patient had to interrupt the treatment | Switch (ADL to SB5) | ||||
IHS4 mean (SD) | ||||||
Baseline: 7.7 [3.1] | ||||||
Week 36: 6.7 [3.3] | ||||||
HiSCR (% achieved): 28.6% | ||||||
DLQI mean (SD) | ||||||
Baseline: 8.6 [1.8] | ||||||
Week 36: 7.3 [1.7] | ||||||
Uveitis | ||||||
Fabiani 2019 [33] | Retrospective study in patients with non-infectious uveitis undergoing the switch from anti-TNFα originator to biosimilar biologic | Identify any change in the control of ocular inflammatory manifestations among patients with non-infectious uveitis switching from an originator to a corresponding anti-TNFα biosimilar | SB5 = 20 patients (33 eyes) | NR | No SB5-specific effectiveness outcome | No SB5-specific safety outcome |
Sota 2021 [34] | Retrospective, nonrandomized study in patients with refractory noninfectious uveitis treated with SB5 | Evaluate the efficacy of SB5 in noninfectious uveitis | SB5 = 26 patients (47 eyes) | Median follow-up: 16.5 months | BCVA mean right eye (SD) | No new ocular complications emerged during the treatment with SB5 |
Baseline: 7.64 [3.69] | ||||||
Last follow-up: 8.89 [2.54] | ||||||
Treatment persistence: 91.8% at 12 and 20 months | BCVA mean left eye (SD) | |||||
Baseline: 7.34 [3.51] | ||||||
Last follow-up: 8.95 [2.44] |
Rheumatologic Diseases
Inflammatory Bowel Diseases
Psoriasis and Hidradenitis Suppurativa
Uveitis
Consistency of Product Quality
Device Features
Product | SB5 | ADL | |
---|---|---|---|
Illustration | |||
Operation step | 2 step | 4 step | |
Button-free operation | Yes | No | |
Needle size | 29G | 27G (LC), 29G (HC) | |
Latex free | Yes | No (LC), Yes (HC) | |
Grip surface (Slip Prevention) | Yes | No | |
Grip shape | Square | Round | |
Audible indicator | Initiation | Yes | Yes |
Completion | Yes | No |