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Current Rheumatology Reports Aug 2018Adalimumab is one of the top-selling drugs worldwide. Its imminent patent expiration has seen the emergence of numerous biosimilar agents. In this article, we recap the... (Review)
Review
PURPOSE OF REVIEW
Adalimumab is one of the top-selling drugs worldwide. Its imminent patent expiration has seen the emergence of numerous biosimilar agents. In this article, we recap the evidence from bio-originator trials in rheumatoid arthritis (RA) to provide context for a critical review of biosimilar trial data.
RECENT FINDINGS
Currently, three adalimumab biosimilars are approved in Europe and/or the USA: Amgen's ABP 501 (AMJEVITA/Solymbic), Boehringer Ingelheim's BI 695501 (Cyltezo) and Samsung Bioepis's SB5 (Imraldi). All three agents met their pre-specified equivalence criteria. Subtle differences in adverse events and clinical responses between the reference and biosimilar products were noted. The introduction of adalimumab biosimilars will offer exciting opportunities in improving treatment access and increasing treatment options for RA and other licensed indications. Real-world data will further provide assurances on efficacy as well as safety.
Topics: Adalimumab; Antirheumatic Agents; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Clinical Trials as Topic; Humans; Treatment Outcome
PubMed: 30094742
DOI: 10.1007/s11926-018-0769-6 -
British Journal of Clinical Pharmacology Feb 2022Adalimumab is a biological therapy used to treat different chronic inflammatory diseases. At present, there is an increasing number of adalimumab biosimilars. To assume... (Review)
Review
AIMS
Adalimumab is a biological therapy used to treat different chronic inflammatory diseases. At present, there is an increasing number of adalimumab biosimilars. To assume the acceptability of interchangeability between reference adalimumab and biosimilars, there should be evidence about efficacy and safety of this switching. Regulation of this practice falls under the authority of individual European Union Member States. The aim of this study is to systematically review the evidence on the efficacy, safety and immunogenicity of switching between reference adalimumab and biosimilars in different chronic immune-mediated inflammatory diseases.
METHODS
Studies presenting data about switching between reference adalimumab and biosimilars were identified by sensitive search strategies in Medline and EMBASE from 1 January 2004 to 30 June 2021.
RESULTS
A total of 471 references were obtained and 21 finally included in the analysis (total number of patients switching: 2802). Eight different adalimumab biosimilars were tested after receiving reference adalimumab. Eight articles included rheumatoid arthritis (RA), one miscellaneous rheumatic disease, six psoriasis (PSO) and six inflammatory bowel disease (IBD) patients. Overall, the efficacy results in the switching groups were comparable to those obtained in the arms of continuous biosimilar and continuous reference adalimumab. There were no significant differences in treatment emergent adverse events, anti-drug or neutralising antibodies among the three groups.
CONCLUSIONS
Switching between reference adalimumab and biosimilars has no impact on efficacy, safety and immunogenicity in patients with RA, PSO and IBD. This finding was consistent for the different adalimumab biosimilars analysed. These conclusions could probably be extended to other rheumatic diseases such as psoriatic arthritis and ankylosing spondylitis.
Topics: Adalimumab; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Chronic Disease; Humans; Inflammatory Bowel Diseases; Psoriasis; Rheumatic Diseases
PubMed: 34622969
DOI: 10.1111/bcp.15101 -
Rheumatology (Oxford, England) May 2024To explore associations between serum adalimumab level, treatment response and drug survival in order to identify optimal drug levels for therapeutic drug monitoring of... (Observational Study)
Observational Study
OBJECTIVES
To explore associations between serum adalimumab level, treatment response and drug survival in order to identify optimal drug levels for therapeutic drug monitoring of adalimumab. Also, to assess the occurrence and risk factors of anti-drug antibody (ADAb) formation.
METHODS
Non-trough adalimumab and ADAb levels were measured by automated fluorescence assays in serum collected after 3 months of adalimumab treatment in patients with RA, PsA or axial SpA (axSpA) included in the observational NOR-DMARD study. Treatment response was evaluated after 3 months and drug survival was evaluated during long-term follow-up.
RESULTS
In 340 patients (97 RA, 69 PsA, 174 axSpA), the median adalimumab level was 7.3 mg/l (interquartile range 4.0-10.3). A total of 33 (10%) patients developed ADAbs. Findings were comparable across diagnoses. In RA and PsA, adalimumab levels ≥6.0 mg/l were associated with treatment response [odds ratio (OR) 2.2 (95% CI 1.0, 4.4)] and improved drug survival [hazard ratio 0.49 (95% CI 0.27, 0.80)]. In axSpA, a therapeutic level could not be identified, but higher adalimumab levels were associated with response. Factors associated with ADAb formation were previous bDMARD use, no methotrexate comedication and the use of adalimumab originator compared with GP2017.
CONCLUSION
Higher adalimumab levels were associated with a better response and improved drug survival for all diagnoses, with a suggested lower threshold of 6.0 mg/l for RA/PsA. This finding, the large variability in drug levels among patients receiving standard adalimumab dose and the high proportion of patients developing ADAbs encourages further investigations into the potential role of therapeutic drug monitoring of adalimumab.
Topics: Humans; Adalimumab; Female; Male; Middle Aged; Antirheumatic Agents; Drug Monitoring; Arthritis, Psoriatic; Adult; Arthritis, Rheumatoid; Treatment Outcome; Aged; Antibodies
PubMed: 37773994
DOI: 10.1093/rheumatology/kead525 -
Arthritis Research & Therapy Apr 2023The objective of this post-hoc analysis was to assess the efficacy and safety of upadacitinib in psoriatic arthritis (PsA) patients with axial involvement. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The objective of this post-hoc analysis was to assess the efficacy and safety of upadacitinib in psoriatic arthritis (PsA) patients with axial involvement.
METHODS
Post-hoc analysis of SELECT-PsA 1 and SELECT-PsA 2 in patients randomized to upadacitinib 15 mg (UPA15), placebo (switched to UPA15 at week 24), or adalimumab 40 mg (ADA; SELECT-PsA 1 only). Axial involvement was determined by investigator judgement (yes or no; based on the totality of available clinical information, such as duration and characteristics of back pain, age of onset, and previous lab investigations and imaging, if available) alone, or investigator judgement and patient-reported outcome (PRO)-based criteria (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4 and BASDAI Q2 ≥ 4). Efficacy outcomes that describe axial disease activity, including BASDAI endpoints, such as change from baseline in the overall BASDAI score or proportion of patients achieving BASDAI50 (≥ 50% improvement from baseline), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints, such as mean change from baseline in overall ASDAS or proportion of patients achieving ASDAS inactive disease or low disease activity, were evaluated at weeks 12, 24, and 56, with nominal P-values shown. Treatment-emergent adverse events (TEAEs) are summarized through week 56.
RESULTS
30.9% of patients in SELECT-PsA 1 and 35.7% in SELECT-PsA 2 had axial involvement by investigator judgement alone; 22.6% (SELECT-PsA 1) and 28.6% (SELECT-PsA 2) had axial involvement by investigator judgement and PRO-based criteria. Greater proportions of patients achieved BASDAI50 with UPA15 versus placebo using either criterion, and versus ADA using investigator judgement alone, at week 24 in SELECT-PsA 1 (investigator alone: UPA15, 59.0%, placebo, 26.9%, P < 0.0001, ADA, 44.1%, P = 0.015; investigator and PRO-based: UPA15, 60.4%, placebo, 29.3%, P < 0.0001, ADA, 47.1%, P = 0.074), with comparable findings in SELECT-PsA 2. Similar results were observed with UPA15 for additional BASDAI and ASDAS endpoints at weeks 12 and 24, with improvements maintained at week 56. Rates of TEAEs were generally similar across sub-groups irrespective of axial involvement status.
CONCLUSIONS
PsA patients with axial involvement determined by predefined criteria showed greater BASDAI and ASDAS responses with UPA15 versus placebo, and numerically similar/greater responses versus ADA. Safety results were generally comparable between patients with or without axial involvement.
TRIAL REGISTRATION
ClinicalTrials.gov: SELECT-PsA 1, NCT03104400; SELECT-PsA 2, NCT0310437.
Topics: Humans; Adalimumab; Arthritis, Psoriatic; Heterocyclic Compounds, 3-Ring; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 37038159
DOI: 10.1186/s13075-023-03027-5 -
Advances in Therapy Oct 2023This study evaluated 12 months adherence and persistence among Janus kinase inhibitors (upadacitinib, baricitinib, tofacitinib) and adalimumab, a tumor necrosis factor...
One-Year Medication Adherence and Persistence in Rheumatoid Arthritis in Clinical Practice: A Retrospective Analysis of Upadacitinib, Adalimumab, Baricitinib, and Tofacitinib.
INTRODUCTION
This study evaluated 12 months adherence and persistence among Janus kinase inhibitors (upadacitinib, baricitinib, tofacitinib) and adalimumab, a tumor necrosis factor inhibitor (TNFi), in patients with rheumatoid arthritis (RA).
METHODS
This retrospective analysis used administrative claims data from the Merative™ MarketScan Research Databases (2018-2022). Eligible adults had ≥ 1 RA diagnosis before the index date, ≥ 1 pharmacy claim for index medication, and ≥ 12 months of continuous insurance enrollment pre- and post-index. Adherence to treatment [defined as proportion of days covered (PDC) ≥ 80%], risk of treatment discontinuation, and mean time to discontinuation were assessed during the 12 months follow-up. Adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI) were reported.
RESULTS
In total, 6317 patients were included (683 upadacitinib, 3732 adalimumab, 132 baricitinib, 1770 tofacitinib). Compared with upadacitinib, patients initiating adalimumab [aOR (95% CI): 0.82 (0.69, 0.96)], baricitinib [0.46 (0.31, 0.68)], and tofacitinib [0.74 (0.62, 0.88)] were significantly less likely to achieve PDC ≥ 80%. Risk of treatment discontinuation was significantly higher in patients treated with adalimumab [aHR (95% CI): 1.14 (1.01, 1.29)], baricitinib [1.48 (1.16, 1.90)], and tofacitinib [1.22 (1.07, 1.38)] compared with upadacitinib. Mean time to discontinuation was 256 (upadacitinib), 249 (adalimumab), 221 (baricitinib), and 239 (tofacitinib) days. Similar results were observed in patients with prior TNFi use.
CONCLUSIONS
Patients with RA, regardless of recent TNFi experience, initiating upadacitinib were significantly more likely to be adherent and less likely to discontinue therapy compared to adalimumab, baricitinib, and tofacitinib in the first 12 months of treatment.
Topics: Adult; Humans; Adalimumab; Antirheumatic Agents; Retrospective Studies; Arthritis, Rheumatoid; Medication Adherence
PubMed: 37542646
DOI: 10.1007/s12325-023-02619-6 -
Nature Communications Jun 2023Biologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this... (Randomized Controlled Trial)
Randomized Controlled Trial
Biologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this randomized trial (Chinese Clinical Trial Registry, ChiCTR2100043061), we assigned 110 patients (27 early-phase and 83 late-phase) to cyclosporine-based immunosuppressant strategy (N = 56) or adalimumab-based biologic strategy (N = 54), each combined with a modified corticosteroid regimen. The primary outcome is change from baseline in best-corrected visual acuity at week 26. The margin of non-inferiority for cyclosporine is -7 letters. The primary outcome is 11.2 letters (95% CI, 7.5 to 14.9) in the cyclosporine group and 6.3 letters (95% CI, 3.1 to 9.6) in the adalimumab group (difference, 4.9; 95% CI, 0.2 to 9.5; P < 0.001 for non-inferiority). The between-group difference is -0.8 letters (95% CI, -6.1 to 4.5) in early-phase disease and 5.7 letters (95% CI, 0.2 to 11.2) in late-phase. Serious adverse events are reported less frequently in the cyclosporine group than in the adalimumab group (0.70 vs. 1.21 events per patient-year). Here, we report that combined with a non-standard corticosteroid regimen, cyclosporine-based immunosuppressant strategy is non-inferior to adalimumab-based biologic strategy by 26 weeks for visual improvement in a cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a late-phase disease.
Topics: Humans; Immunosuppressive Agents; Uveomeningoencephalitic Syndrome; Adalimumab; Cyclosporine; Biological Products
PubMed: 37355662
DOI: 10.1038/s41467-023-39483-5 -
BMC Ophthalmology May 2023To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU).
METHODS
We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated.
RESULTS
Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab.
CONCLUSION
Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.
Topics: Humans; Adalimumab; Infliximab; Antibodies, Monoclonal; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal, Humanized; Tumor Necrosis Factor-alpha; Uveitis; Inflammation
PubMed: 37248486
DOI: 10.1186/s12886-023-02987-1 -
Clinical and Translational Science May 2020This study aimed at exploring the concentration-effect relationship of adalimumab and early adalimumab and anti-adalimumab antibody (AAA) levels in predicting primary... (Observational Study)
Observational Study
This study aimed at exploring the concentration-effect relationship of adalimumab and early adalimumab and anti-adalimumab antibody (AAA) levels in predicting primary nonresponse in a real-world pilot cohort of patients with ankylosing spondylitis. Thirty-one patients were included. The Ankylosing Spondylitis Disease Activity Score improved with increasing adalimumab trough level at week 12 and reached a major improvement with levels between 8 and 12 μg/mL. Moreover, weeks 4 and 2 adalimumab levels below 4.28 and 3.37 μg/mL were predictive of primary nonresponse (area under the curve (AUC) = 0.89, 0.88; P = 0.0003, P = 0.034, respectively). Week 4 AAA signal-to-noise levels were significantly higher among primary nonresponders, and the cutoff for primary nonresponse prediction was above 5.31 (AUC = 0.81; P = 0.004). Adalimumab trough levels in a range of 8-12 μg/mL are optimum to reach major improvement, and lower adalimumab with higher AAA levels at the early stage (week 4) predict primary nonresponse by supporting proactive monitoring to optimize adalimumab therapy.
Topics: Adalimumab; Adult; Antibodies; Antirheumatic Agents; Area Under Curve; Cohort Studies; Drug Resistance; Female; Humans; Male; Prognosis; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 31961477
DOI: 10.1111/cts.12738 -
Health Technology Assessment... Nov 2017Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biological drugs.
OBJECTIVES
To evaluate the clinical effectiveness and cost-effectiveness of subcutaneous adalimumab (Humira; AbbVie Ltd, Maidenhead, UK) and a dexamethasone intravitreal implant (Ozurdex; Allergan Ltd, Marlow, UK) in adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis.
DATA SOURCES
Electronic databases and clinical trials registries including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and the World Health Organization's International Clinical Trials Registry Platform were searched to June 2016, with an update search carried out in October 2016.
REVIEW METHODS
Review methods followed published guidelines. A Markov model was developed to assess the cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from a NHS and Personal Social Services (PSS) perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken.
RESULTS
Of the 134 full-text articles screened, three studies (four articles) were included in the clinical effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with limited standard care also provided in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer in the adalimumab group than in the placebo group, with a hazard ratio of 0.50 [95% confidence interval (CI) 0.36 to 0.70; < 0.001] in the VISUAL I trial and 0.57 (95% CI 0.39 to 0.84; = 0.004) in the VISUAL II trial. The adalimumab group showed a significantly greater improvement than the placebo group in the 25-item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial (mean difference 4.20; = 0.010) but not the VISUAL II trial (mean difference 2.12; = 0.16). Some systemic adverse effects occurred more frequently with adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single 0.7-mg dexamethasone implant against a sham procedure, with limited standard care also provided in both arms. Dexamethasone provided significant benefits over the sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous haze score of zero ( < 0.014), the mean best corrected visual acuity improvement ( ≤ 0.002) and the percentage of patients with a ≥ 5-point improvement in VFQ-25 score ( < 0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than with the sham procedure. The incremental cost-effectiveness ratio (ICER) for one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis compared with limited current practice, as per the HURON trial, was estimated to be £19,509 per quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis compared with limited current practice, as per the VISUAL trials, was estimated to be £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggested that the rate of blindness has the biggest impact on the model results. The interventions may be more cost-effective in populations in which there is a greater risk of blindness.
LIMITATIONS
The clinical trials did not fully reflect clinical practice. Thirteen additional studies of clinically relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain because of the limited evidence base.
CONCLUSIONS
Two RCTs of systemic adalimumab and one RCT of a unilateral, single dexamethasone implant showed significant benefits over placebo or a sham procedure. The ICERs for adalimumab were estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was estimated to fall below standard thresholds. However, there is substantial uncertainty around the model assumptions. In future work, primary research should compare dexamethasone and adalimumab with current treatments over the long term and in important subgroups and consider how short-term improvements relate to long-term effects on vision.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42016041799.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Cost-Benefit Analysis; Dexamethasone; Humans; Quality-Adjusted Life Years; Technology Assessment, Biomedical; Uveitis, Intermediate; Uveitis, Posterior
PubMed: 29183563
DOI: 10.3310/hta21680 -
Inflammopharmacology Jun 2023Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in... (Review)
Review
Psoriasis represents an immune-mediated disease with an unclear cause that's marked by inflammation triggered by dysfunction in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious role in the pathogenesis of psoriasis, in addition to specific immunological molecules such as TNF-, IL-12, IL-23, IL-17, and other molecules that can aid in the pathogenesis of psoriasis. So, during the past two decades, biologists have created chemical drugs that target these cells or molecules and therefore prevent the disease from occurring. Alefacept, efalizumab, Adalimumab, Ustekinumab, and Secukinumab are a few examples of chemical drugs. It was discovered that these chemical drugs have long-term side effects that can cause defects in the patient's body, such as the development of the rare but life-threatening disorder progressive multifocal leukoencephalopathy (PCL). Its rapidly progressive infection of the central nervous system caused by the JC virus and other drugs may cause increased production of neutralising anti-drug antibodies (ADA) and the risk of infusion reactions like pruritus, flushing, hypertension, headache, and rash. So, our context intends to talk in our review about natural products or plants that may have therapeutic characteristics for this disease and may have few or no side effects on the patient's body.
Topics: Humans; Middle Aged; Antibodies, Monoclonal; Psoriasis; Adalimumab; Interleukin-12; Inflammation
PubMed: 36995575
DOI: 10.1007/s10787-023-01178-0