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Advances in Clinical and Experimental... Oct 2020Non-infectious uveitis (NIU) is a serious sight-threatening condition whose pathogenesis is often autoimmune in nature. It may manifest in any age group, though adults... (Review)
Review
Non-infectious uveitis (NIU) is a serious sight-threatening condition whose pathogenesis is often autoimmune in nature. It may manifest in any age group, though adults aged 20-50 are the group most often affected. It causes 5-10% of visual impairment worldwide. The epidemiology of some specific uveitis diseases varies worldwide, because they are influenced by genetic, environmental and socioeconomic factors. It can occur only in the eye or as a symptom of a systemic condition. The most common cause of NIU is HLA-B-27-associated anterior uveitis (4-32%). The standard treatment for NIU is a local, topical and systemic steroid therapy in combination with immunomodulatory therapy. However, recently, a new drug - adalimumab, which is a tumor necrosis factor α (TNF-α) inhibitor - was approved by FDA in the treatment of NIU and is increasingly used to treat various conditions. Adalimumab has been proven in many studies to be safe and effective in the treatment of NIU associated with diverse systemic diseases.
Topics: Acute Disease; Adalimumab; Humans; Tumor Necrosis Factor-alpha; Uveitis
PubMed: 33125196
DOI: 10.17219/acem/125431 -
The New England Journal of Medicine Jul 2021Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the tumor necrosis factor inhibitor adalimumab in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
METHODS
We randomly assigned patients with moderate-to-severe plaque psoriasis in a 1:1:1 ratio to receive subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at a dose of 320 mg every 4 weeks for 16 weeks, then every 8 weeks for weeks 16 to 56; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56. The primary end points were a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI 90 response; PASI scores range from 0 to 72, with higher scores indicating worse disease) and an Investigator's Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (scores range from 0 [clear skin] to 4 [severe disease]), at week 16. The analysis of the primary end points tested noninferiority at a margin of -10 percentage points and then tested for superiority.
RESULTS
A total of 614 patients were screened, and 478 were enrolled; 158 patients were assigned to receive bimekizumab every 4 weeks, 161 to receive bimekizumab every 4 weeks and then every 8 weeks, and 159 to receive adalimumab. The mean age of the patients was 44.9 years; the mean PASI score at baseline was 19.8. At week 16, a total of 275 of 319 patients (86.2%) who received bimekizumab (both dose groups combined) and 75 of 159 (47.2%) who received adalimumab had a PASI 90 response (adjusted risk difference, 39.3 percentage points; 95% confidence interval [CI], 30.9 to 47.7; P<0.001 for noninferiority and superiority). A total of 272 of 319 patients (85.3%) who received bimekizumab and 91 of 159 (57.2%) who received adalimumab had an IGA score of 0 or 1 (adjusted risk difference, 28.2 percentage points; 95% CI, 19.7 to 36.7; P<0.001 for noninferiority and superiority). The most common adverse events with bimekizumab were upper respiratory tract infections, oral candidiasis (predominantly mild or moderate as recorded by the investigator), hypertension, and diarrhea.
CONCLUSIONS
In this 56-week trial, bimekizumab was noninferior and superior to adalimumab through 16 weeks in reducing symptoms and signs of plaque psoriasis but was associated with a higher frequency of oral candidiasis and diarrhea. Longer and larger trials are required to determine the efficacy and safety of bimekizumab as compared with other agents in the treatment of plaque psoriasis. (Funded by UCB Pharma; BE SURE ClinicalTrials.gov number, NCT03412747.).
Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Candidiasis, Oral; Diarrhea; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Interleukin-17; Male; Middle Aged; Psoriasis; Severity of Illness Index
PubMed: 33891379
DOI: 10.1056/NEJMoa2102388 -
Frontiers in Immunology 2021Adalimumab, as a TNF inhibitor biologic for the treatment of rheumatoid arthritis, is one of the top-selling drugs worldwide. As its various patents have gradually... (Review)
Review
Adalimumab, as a TNF inhibitor biologic for the treatment of rheumatoid arthritis, is one of the top-selling drugs worldwide. As its various patents have gradually expired, experiments on its biosimilars are constantly being implemented. In this review, we summarized clinical trials of seven biosimilars currently approved by the FDA and/or EMA for the treatment of rheumatoid arthritis, namely: ABP 501 (Amjevita/Amgevita/Solymbic), BI 695501 (Cyltezo), SB5 (Imraldi/Hadlima), GP2017 (Hyrimoz/Hefiya/Halimatoz), MSB11022 (Idacio), FKB327 (Hulio), and PF-06410293 (Abrilada). Overall, these biosimilars showed similar efficacy, safety, and immunogenicity to adalimumab. All biosimilar switching trials indicated that switching from adalimumab to a biosimilar does not have a significant impact on efficacy, safety, and immunogenicity.
Topics: Adalimumab; Antirheumatic Agents; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Clinical Trials as Topic; Humans
PubMed: 33889152
DOI: 10.3389/fimmu.2021.638444 -
Lancet (London, England) May 2020Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response.
METHODS
This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080.
FINDINGS
Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator.
INTERPRETATION
Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis.
FUNDING
Novartis Pharma.
Topics: Adalimumab; Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Clinical Decision-Making; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Safety; Treatment Outcome
PubMed: 32386593
DOI: 10.1016/S0140-6736(20)30564-X -
The New England Journal of Medicine Sep 2016Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.
METHODS
This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported.
RESULTS
The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years).
CONCLUSIONS
In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).
Topics: Adalimumab; Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Treatment Failure; Uveitis; Vision Disorders; Young Adult
PubMed: 27602665
DOI: 10.1056/NEJMoa1509852 -
Frontiers in Immunology 2022Although the introduction of tumor necrosis factor (TNF) inhibitors represented a significant advance in the treatment of rheumatoid arthritis (RA), traditional...
Ozoralizumab, a Humanized Anti-TNFα NANOBODY Compound, Exhibits Efficacy Not Only at the Onset of Arthritis in a Human TNF Transgenic Mouse but Also During Secondary Failure of Administration of an Anti-TNFα IgG.
Although the introduction of tumor necrosis factor (TNF) inhibitors represented a significant advance in the treatment of rheumatoid arthritis (RA), traditional anti-TNFα antibodies are somewhat immunogenic, and their use results in the formation of anti-drug antibodies (ADAs) and loss of efficacy (secondary failure). Ozoralizumab is a trivalent, bispecific NANOBODY compound that differs structurally from IgGs. In this study we investigated the suppressant effect of ozoralizumab and adalimumab, an anti-TNFα IgG, on arthritis and induction of ADAs in human TNF transgenic mice. Ozoralizumab markedly suppressed arthritis progression and did not induce ADAs during long-term administration. We also developed an animal model of secondary failure by repeatedly administering adalimumab and found that switching from adalimumab to ozoralizumab was followed by superior anti-arthritis efficacy in the secondary-failure animal model. Moreover, ozoralizumab did not form large immune complexes that might lead to ADA formation. The results of our studies suggest that ozoralizumab, which exhibited low immunogenicity in the animal model used and has a different antibody structure from that of IgGs, is a promising candidate for the treatment of RA patients not only at the onset of RA but also during secondary failure of anti-TNFα treatment.
Topics: Adalimumab; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Humans; Immunoglobulin G; Mice; Mice, Transgenic; Tumor Necrosis Factor Inhibitors
PubMed: 35273620
DOI: 10.3389/fimmu.2022.853008 -
Scientific Reports Oct 2022In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the...
In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the subcutaneous injection. To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. Alexa Fluor 680-labeled ozoralizumab and adalimumab were administered by subcutaneous injection once (2 mg/kg) at five weeks after induction of collagen-induced arthritis (CIA) in an animal arthritis model. The time-course of changes in the fluorescence intensities of the two compounds in the paws and serum were evaluated. The paws of the CIA mice were harvested at four and eight hours after the injection for fluorescence microscopy. Biofluorescence imaging revealed better distribution of ozoralizumab to the joint tissues than of adalimumab, as early as at four hours after the injection. Fluorescence microscopy revealed a greater fluorescence intensity of ozoralizumab in the joint tissues than that of adalimumab at eight hours after the injection. Ozoralizumab showed a significantly higher absorption rate constant as compared with adalimumab. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice.
Topics: Mice; Animals; Arthritis, Experimental; Adalimumab; Tumor Necrosis Factor Inhibitors; Tissue Distribution; Tumor Necrosis Factor-alpha; Antibodies, Monoclonal; Disease Models, Animal
PubMed: 36302840
DOI: 10.1038/s41598-022-23152-6 -
Clinical Drug Investigation Oct 2022AVT02 (Hukyndra, Libmyris) is a biosimilar of the reference anti-tumour necrosis factor alpha monoclonal antibody adalimumab. It is approved for use in all indications... (Review)
Review
AVT02 (Hukyndra, Libmyris) is a biosimilar of the reference anti-tumour necrosis factor alpha monoclonal antibody adalimumab. It is approved for use in all indications for which reference adalimumab is approved. AVT02 has similar physicochemical and pharmacodynamic properties to those of reference adalimumab, and the pharmacokinetic similarity of the agent has been shown in healthy adult subjects. AVT02 demonstrated clinical efficacy similar to that of reference adalimumab in patients with chronic plaque psoriasis, and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of AVT02 were similar to those of reference adalimumab. Switching from reference adalimumab to AVT02 appeared to have no impact on efficacy, safety or immunogenicity. The role of reference adalimumab in the management of immune-mediated inflammatory diseases is well established and AVT02 provides an effective biosimilar alternative for patients requiring adalimumab therapy.
Topics: Adalimumab; Adult; Biosimilar Pharmaceuticals; Humans; Psoriasis
PubMed: 36181655
DOI: 10.1007/s40261-022-01196-w -
Lancet (London, England) Aug 2019Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed... (Comparative Study)
Comparative Study Randomized Controlled Trial
Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial.
BACKGROUND
Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis.
METHODS
IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16-44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523.
FINDINGS
Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5-32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6-30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9-61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B.
INTERPRETATION
Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis.
FUNDING
AbbVie and Boehringer Ingelheim.
Topics: Adalimumab; Adult; Antibodies, Monoclonal; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Psoriasis
PubMed: 31280967
DOI: 10.1016/S0140-6736(19)30952-3 -
BioDrugs : Clinical Immunotherapeutics,... Feb 2019FKB327 (Hulio) is a biosimilar of the reference monoclonal anti-TNFα antibody adalimumab, and is approved in the EU for use in the same indications as reference... (Review)
Review
FKB327 (Hulio) is a biosimilar of the reference monoclonal anti-TNFα antibody adalimumab, and is approved in the EU for use in the same indications as reference adalimumab. FKB327 has similar physicochemical and pharmacodynamic properties to those of reference adalimumab, and pharmacokinetic equivalence was shown in healthy volunteers and patients with moderate-to-severe rheumatoid arthritis (RA) despite methotrexate therapy. FKB327 demonstrated equivalent clinical efficacy to that of reference adalimumab in patients with moderate-to-severe RA, and similar tolerability, safety and immunogenicity profiles. Switching from reference adalimumab to FKB327 had no impact on efficacy, safety or immunogenicity.
Topics: Adalimumab; Antirheumatic Agents; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Humans; Methotrexate; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha
PubMed: 30712241
DOI: 10.1007/s40259-019-00335-8