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Arthritis Research & Therapy Oct 2022We compared the treatment effectiveness between guselkumab and adalimumab in patients with pustulotic arthro-osteitis (PAO). In addition, we performed peripheral blood...
OBJECTIVES
We compared the treatment effectiveness between guselkumab and adalimumab in patients with pustulotic arthro-osteitis (PAO). In addition, we performed peripheral blood immunophenotyping to elucidate the immunological background and analyzed the impact of therapeutic drugs to verify the validity of immunological phenotypes as therapeutic targets.
METHODS
Patients were treated with guselkumab 100 mg (guselkumab group; n = 12) and adalimumab 40 mg (adalimumab group; n = 13). Arthritis disease activity, skin lesion activity, and patient-reported outcomes (PROs) were evaluated and compared between the two groups. The retention rate and adverse events were evaluated. Comprehensive phenotyping of peripheral immune cells was performed in both groups, and phenotypes were compared before and after treatment.
RESULTS
At 6 months, both groups showed significant improvement in arthritis disease activity and PROs. In the guselkumab group, skin symptoms significantly improved. The 6-month continuation rates were 91.7% (11/12) and 69.2% (9/13) in the guselkumab and adalimumab groups, respectively. Adverse events occurred in 2/12 and 5/13 patients in the guselkumab (16.7%) and adalimumab (38.5%) groups, respectively. Peripheral blood immunophenotyping showed that the proportion of activated T helper (Th) 1 cells was significantly lower in patients with PAO than in healthy controls and that the proportion of activated Th17 cells was significantly higher in patients with PAO, which significantly decreased after treatment with guselkumab.
CONCLUSION
Although guselkumab and adalimumab have comparable efficacy for PAO, their impact on immunophenotypes varies.
Topics: Humans; Adalimumab; Osteitis; Psoriasis; Immunophenotyping; Arthritis
PubMed: 36303202
DOI: 10.1186/s13075-022-02934-3 -
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 -
Actas Dermo-sifiliograficas Oct 2023Hidradenitis suppurativa (HS) is a chronic inflammatory entity characterized by the appearance of multiple nodules, abscesses, and fistulas, predominantly in apocrine... (Review)
Review
Hidradenitis suppurativa (HS) is a chronic inflammatory entity characterized by the appearance of multiple nodules, abscesses, and fistulas, predominantly in apocrine regions. In addition to its dermatological involvement, it is associated with multiple systemic comorbidities. Its treatment is combined: topical pharmacological, systemic pharmacological and surgical. Regarding biologic or small molecule drugs, currently only adalimumab is approved. A narrative review of the literature on biological or small molecule drugs used in the treatment of hidradenitis suppurativa is presented. The arsenal we found is large, with multiple targets: inhibitors of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-17, IL-23, IL-1, inhibitors of the janus kinase (JAK) pathway, and multiple other drugs in study. New prospective studies and comparative trials are needed to analyze the effectiveness and safety of these treatments, in an entity with a promising future.
Topics: Humans; Hidradenitis Suppurativa; Prospective Studies; Adalimumab; Tumor Necrosis Factor-alpha; Biological Products
PubMed: 37541580
DOI: 10.1016/j.ad.2023.08.001 -
RMD Open May 2024To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years.
METHODS
Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed).
RESULTS
Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192.
CONCLUSION
The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment.
TRIAL REGISTRATION NUMBER
NCT02629159.
Topics: Humans; Arthritis, Rheumatoid; Adalimumab; Heterocyclic Compounds, 3-Ring; Female; Antirheumatic Agents; Male; Middle Aged; Treatment Outcome; Double-Blind Method; Adult; Methotrexate; Aged; Drug Therapy, Combination
PubMed: 38806190
DOI: 10.1136/rmdopen-2023-004007 -
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 -
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 -
The Journal of Dermatological Treatment Dec 2023Tumor necrosis factor (TNF) inhibitors improved clinical outcomes for patients with psoriasis but are limited by their high cost. There are several biosimilar options... (Review)
Review
Tumor necrosis factor (TNF) inhibitors improved clinical outcomes for patients with psoriasis but are limited by their high cost. There are several biosimilar options approved for the treatment of psoriasis which provides a lower-cost alternative and the potential to increase treatment availability for both biologically naïve and bioexperienced patients. Numerous phase III randomized controlled trials (RCTs) have investigated the effects of switching from biologics to biosimilars; biosimilars had comparable safety and efficacy to their reference products. Real-world evidence may provide complementary information on the expected performance of biosimilars. In this literature review, we analyzed data from real-world studies on switching from biologics for psoriasis to their biosimilars. Effectiveness and safety profiles were comparable when switching from biologics to biosimilars of adalimumab, etanercept, and infliximab. These studies are limited by their sample sizes, duration of follow-up, and single-arm designs without control groups. Based on available real-world evidence, patients may safely and effectively undergo switching to biosimilar therapies for the treatment of psoriasis.
Topics: Humans; Biosimilar Pharmaceuticals; Infliximab; Etanercept; Adalimumab; Biological Factors; Tumor Necrosis Factor Inhibitors; Psoriasis
PubMed: 36305624
DOI: 10.1080/09546634.2022.2140569 -
RMD Open Sep 2022Post hoc analysis of pooled data from nine randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid... (Clinical Trial)
Clinical Trial
OBJECTIVE
Post hoc analysis of pooled data from nine randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) on residual pain in patients with RA or PsA with abrogated inflammation.
METHODS
Patients who received ≥1 dose of tofacitinib 5 mg twice daily, adalimumab or placebo with/without background conventional synthetic disease-modifying antirheumatic drugs and had abrogated inflammation (swollen joint count (SJC)=0 and C reactive protein (CRP)<6 mg/L) after 3 months' therapy were included. Assessments included Patient's Assessment of Arthritis Pain at month 3 (Visual Analogue Scale [VAS] 0-100 mm). Scores were summarised descriptively; treatment comparisons assessed by Bayesian network meta-analyses (BNMA).
RESULTS
From the total population with RA/PsA, 14.9% (382 of 2568), 17.1% (118 of 691) and 5.5% (50 of 909) of patients receiving tofacitinib, adalimumab and placebo, respectively, had abrogated inflammation after 3 months' therapy. Patients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had higher baseline CRP versus placebo; patients with RA receiving tofacitinib/adalimumab had lower SJC and longer disease duration versus placebo. Median residual pain (VAS) at month 3 was 17.0, 19.0 and 33.5 in patients with RA treated with tofacitinib, adalimumab or placebo, and 24.0, 21.0 and 27.0 in patients with PsA, respectively. Residual pain reductions with tofacitinib/adalimumab versus placebo were less prominent in patients with PsA versus patients with RA, with no significant differences between tofacitinib/adalimumab, per BNMA.
CONCLUSION
Patients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had greater residual pain reduction versus placebo at month 3. Results were similar between tofacitinib and adalimumab.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov registry (NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT01877668; NCT01882439).
Topics: Humans; Adalimumab; Arthritis, Psoriatic; Arthritis, Rheumatoid; Bayes Theorem; C-Reactive Protein; Inflammation; Pyrroles; Treatment Outcome
PubMed: 36814062
DOI: 10.1136/rmdopen-2022-002478 -
Advances in Therapy Feb 2024SB5 is an approved biosimilar of adalimumab, a recombinant monoclonal anti-tumor necrosis factor (TNF) antibody. The approval of SB5 was based on the comparison with... (Review)
Review
SB5 is an approved biosimilar of adalimumab, a recombinant monoclonal anti-tumor necrosis factor (TNF) antibody. The approval of SB5 was based on the comparison with reference adalimumab in analytical studies, pharmacokinetic (PK) and immunogenicity assessments, and randomized controlled trials. Efficacy data was primarily obtained in patients with rheumatoid arthritis, and extended to include additional indications such as psoriasis, Crohn's disease, or ulcerative colitis by extrapolation. Following its approval, additional post-marketing data have been collected comparing SB5 with reference adalimumab. This review summarizes the clinical data on SB5 from randomized controlled trials and provides a comprehensive overview of the available post-approval data. In "real-world" settings, SB5 was as effective as its reference product across different indications and countries, treatment persistence was well maintained throughout studies, and no new safety concerns were identified. In both controlled and "real-world" settings, switching from reference adalimumab to SB5 was not associated with altered efficacy or clinical complications. In post-approval studies, the quality of SB5 was consistent over time, independent of the batch and process changes, and the SB5 autoinjector was preferred over other autoinjectors by both healthcare professionals and patients. Taken together, these data support the use of SB5 whenever reference adalimumab is appropriate and demonstrate that switching from reference adalimumab to SB5 is feasible.
Topics: Humans; Adalimumab; Biosimilar Pharmaceuticals; Arthritis, Rheumatoid; Crohn Disease; Tumor Necrosis Factor-alpha; Treatment Outcome
PubMed: 38110655
DOI: 10.1007/s12325-023-02737-1 -
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