-
Frontiers in Pharmacology 2024To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA).
OBJECTIVE
To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA).
METHODS
Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality.
RESULTS
A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215]).
CONCLUSION
Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.
PubMed: 38881871
DOI: 10.3389/fphar.2024.1370661 -
BMC Neurology Jun 2024We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of... (Review)
Review
BACKGROUND
We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet's. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic.
CASE
The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet's disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity.
LITERATURE REVIEW
We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later.
CONCLUSION
As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.
Topics: Humans; Female; Adult; Intracranial Hypertension; Behcet Syndrome; Antibodies, Monoclonal, Humanized; Immunosuppressive Agents
PubMed: 38877431
DOI: 10.1186/s12883-024-03708-x -
PloS One 2024This observational study evaluated the impact of a sponsor company-provided Patient Support Program (PSP) on discontinuation of adalimumab in adult Australian patients... (Observational Study)
Observational Study
Impact of a Patient Support Program on time to discontinuation of adalimumab in Australian adult patients with immune-mediated inflammatory diseases-an observational study.
This observational study evaluated the impact of a sponsor company-provided Patient Support Program (PSP) on discontinuation of adalimumab in adult Australian patients eligible for Pharmaceutical Benefit Scheme (PBS)-reimbursed adalimumab for Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Crohn's Disease (CD), Ulcerative Colitis (UC), or Hidradenitis Suppurativa (HS). Patients initiating adalimumab between May 2018 and September 2019 were enrolled into two prospective cohorts based on their decision to opt for or decline the PSP (PSP or non-PSP cohorts). In addition, a historical, retrospective Non-PSP cohort was established from the Services Australia 10% PBS dataset by extracting data of patients initiating adalimumab prior to the introduction of adalimumab PSPs and based on adalimumab PBS listing dates (AS: April 2007 to March 2009; PsA/RA: January 2007 to December 2008; CD: January 2009 to December 2010; HS and UC indications not included). Follow-up for all cohorts was 12 months. The primary endpoint was the time to discontinuation, compared between the prospective PSP cohort and the prospective or retrospective Non-PSP cohort. Inverse probability of treatment weighting was used to balance the cohorts. A Cox proportional hazards model indicated no difference in time to discontinuation between the prospective PSP (n = 162) and non-PSP (n = 65) cohorts (HR [95% CI] = 1.256 [0.616-2.563], p = 0.5304). The 12-month adalimumab persistence rates (95% CI) were 78% (69%, 84%) and 82% (67%, 90%), respectively. In contrast, discontinuation was less likely in the prospective PSP (n = 151) compared with the retrospective non-PSP (n = 297) cohort (HR [95% CI] = 0.44 [0.28-0.68], p<0.001). The 12-month persistence rates (95% CI) were 81% (76%, 90%) and 61% (56%, 67%), respectively. Overall, this study suggests that optimal adalimumab persistence can be achieved with either a structured PSP or healthcare support from other sources, but this was not the case more than a decade ago.
Topics: Humans; Adalimumab; Female; Male; Adult; Middle Aged; Australia; Retrospective Studies; Prospective Studies; Antirheumatic Agents; Spondylitis, Ankylosing; Aged; Withholding Treatment
PubMed: 38870244
DOI: 10.1371/journal.pone.0300624 -
Journal of Atherosclerosis and... Jun 2024Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory.
AIM
Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory.
METHODS
A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) database. Cardiovascular AEs associated with TNF-α inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) were evaluated using a disproportionality analysis. To reduce potential confounders, adjusted ROR and subgroup analyses were performed.
RESULTS
After excluding duplicates, 9,817 cardiovascular reports were associated with the five TNF-α inhibitors. Only adalimumab had positive signals for myocardial infarction (ROR=1.58, 95%CI=1.51-1.64) and arterial thrombosis (ROR=1.54, 95%CI=1.49-1.58). The remaining four TNF-α inhibitors did not show a risk association with any type of cardiovascular event. Further analyses of specific indication subgroups and after adjusting for any confounding factors demonstrated that adalimumab was still significantly associated with cardiovascular events, especially in patients with psoriasis (adjusted ROR=2.16, 95%CI=1.95-2.39).
CONCLUSIONS
This study revealed that adalimumab was the only TNF-α inhibitor associated with an elevated risk of thrombotic cardiovascular AEs, whereas the other four TNF-α inhibitors did not show any risk effect. However, given the limitations of such pharmacovigilance studies, it is necessary to validate these findings in prospective studies in the future.
PubMed: 38866553
DOI: 10.5551/jat.64767 -
Cell Jun 2024Ongoing, early-stage clinical trials illustrate the translational potential of human pluripotent stem cell (hPSC)-based cell therapies in Parkinson's disease (PD)....
Ongoing, early-stage clinical trials illustrate the translational potential of human pluripotent stem cell (hPSC)-based cell therapies in Parkinson's disease (PD). However, an unresolved challenge is the extensive cell death following transplantation. Here, we performed a pooled CRISPR-Cas9 screen to enhance postmitotic dopamine neuron survival in vivo. We identified p53-mediated apoptotic cell death as a major contributor to dopamine neuron loss and uncovered a causal link of tumor necrosis factor alpha (TNF-α)-nuclear factor κB (NF-κB) signaling in limiting cell survival. As a translationally relevant strategy to purify postmitotic dopamine neurons, we identified cell surface markers that enable purification without the need for genetic reporters. Combining cell sorting and treatment with adalimumab, a clinically approved TNF-α inhibitor, enabled efficient engraftment of postmitotic dopamine neurons with extensive reinnervation and functional recovery in a preclinical PD mouse model. Thus, transient TNF-α inhibition presents a clinically relevant strategy to enhance survival and enable engraftment of postmitotic hPSC-derived dopamine neurons in PD.
PubMed: 38866017
DOI: 10.1016/j.cell.2024.05.030 -
PharmacoEconomics - Open Jun 2024Today, there are many treatment options available for the management of ulcerative colitis, creating challenges in selecting the most efficacious and cost-effective...
BACKGROUND
Today, there are many treatment options available for the management of ulcerative colitis, creating challenges in selecting the most efficacious and cost-effective treatment sequences. Treatments in the anti-tumor necrosis factor alpha (TNFα) therapeutic class, as well as vedolizumab, are widely used and endorsed as first-line options according to treatment guidelines. The aim of this study was to compare treatment sequences involving vedolizumab and the anti-TNFα treatment adalimumab in terms of cost-effectiveness in the treatment of moderately to severely active ulcerative colitis in Italy.
METHODS
A cost-effectiveness model comparing treatment sequences within the Italian National Health Service in terms of costs and quality-adjusted life years (QALYs) with a lifetime horizon was developed. The analysis focused on the relative positioning of vedolizumab and adalimumab, leveraging the results of the landmark head-to-head VARSITY clinical trial as key inputs. The robustness of the results was investigated through a range of sensitivity and scenario analyses.
RESULTS
The strategy of vedolizumab as a first-line advanced therapy followed by adalimumab was associated with higher costs and health benefits compared with first-line adalimumab followed by vedolizumab. The incremental cost-effectiveness ratio was €16,146/QALY, which was found to be robust to changes to inputs associated with areas of high uncertainty.
CONCLUSION
This economic evaluation estimated a 94% probability that vedolizumab as a first-line advanced therapy is cost-effective at a threshold of €33,004/QALY when compared with first-line adalimumab sequences. Using clinical trial evidence to inform the efficacy of second-line treatments estimated that the effectiveness of anti-TNFα treatments is not substantially reduced by vedolizumab exposure.
PubMed: 38858333
DOI: 10.1007/s41669-024-00497-4 -
Journal of Clinical Medicine Research May 2024Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable...
Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.
PubMed: 38855784
DOI: 10.14740/jocmr5165 -
Patient Preference and Adherence 2024Medication delivery device design impacts treatment satisfaction, adherence, and compliance in patients receiving biologics. This survey assessed autoinjector attributes...
PURPOSE
Medication delivery device design impacts treatment satisfaction, adherence, and compliance in patients receiving biologics. This survey assessed autoinjector attributes that are important to patients, and assessed patient perceptions and preferences between an adalimumab biosimilar autoinjector (Hyrimoz SensoReady Pen [SDZ-ADL pen]) and the reference adalimumab autoinjector (Humira Pen [ref-ADL pen]) in patients with rheumatoid arthritis (RA) or Crohn's disease (CD) in Canada.
PATIENTS AND METHODS
In this survey, adult patients were recruited for web-assisted telephone interviews. Patients had ≥ 3 months' experience with the ref-ADL pen and 1-12 months' experience with the SDZ-ADL pen.
RESULTS
The survey included 120 patients with RA (n = 32) or CD (n = 88). Mean experience with the ref-ADL pen was 7 years for RA or 5 years for CD vs 9 months with the SDZ-ADL pen. The most important autoinjector attributes were the ability to use the pen independently and the ease and simplicity of self-injection. When comparing the two autoinjectors, patients significantly preferred the SDZ-ADL pen over the ref-ADL pen for nearly every attribute evaluated, with the greatest differences reported for visual and audible feedback mechanisms, ease of self-injection, and ability to use the device independently. Overall, 82% of patients preferred the SDZ-ADL pen over the ref-ADL pen, with buttonless activation and less injection pain being the main drivers for this preference.
CONCLUSION
Patients with RA or CD indicated a preference for the SDZ-ADL pen over the ref-ADL pen, independent of the duration of use of the pen. The preference for a biosimilar device within 1 year of switching provides reassurance of rapid patient acceptance of biosimilars and may simplify the switching process. These results confirm the importance of ensuring autoinjector design supports independent self-administration of medication and align with previous data showing high patient satisfaction with the SDZ-ADL pen.
PubMed: 38854477
DOI: 10.2147/PPA.S455791 -
BMC Ophthalmology Jun 2024This study explores prognostic factors influencing Vogt-Koyanagi-Harada (VKH) disease and observes the efficacy and safety of Adalimumab (ADA) in treating recurrence in...
BACKGROUND
This study explores prognostic factors influencing Vogt-Koyanagi-Harada (VKH) disease and observes the efficacy and safety of Adalimumab (ADA) in treating recurrence in Vogt-Koyanagi-Harada (VKH) patients.
METHODS
A retrospective study was conducted on all patients diagnosed with VKH disease at Beijing Tongren Hospital between 2020 and 2023. Clinical data included initial and final visual acuity, age, gender, ocular complications, treatment modalities, disease duration, and recurrence frequency.
RESULTS
A total of 62 VKH patients were included, comprising 34 in the acute-resolved group and 28 in the chronic-recurrent group. The mean age of patients in the acute-resolved group was 38.29 ± 15.46 years, while the mean age of chronic-recurrent group had a 49.00 ± 16.43 years. Initial best-corrected visual acuity (BCVA) examination at the first visit showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002). During follow-up, ocular complications were observed in 29.4% of the acute-resolved group patients and 41.7% of the chronic-recurrent group patients (P = 0.006). "Sunset glow fundus" was observed in 23.5% of the acute-resolved group and 64.3% of the chronic-recurrent group patients (P = 0.001). Poor initial BCVA (P = 0.046) and the occurrence of "sunset glow fundus" (P = 0.040) were significantly associated with progression to the chronic recurrent phase. Logistic regression analysis revealed that older age at onset (P = 0.042) and the occurrence of "sunset glow fundus" (P = 0.037) were significant predictors for progression to the chronic recurrent phase. ADA significantly reduced anterior chamber inflammatory cells (P = 0.000) and vitreous cavity inflammatory cells (P = 0.001) in the chronic-recurrent group, and markedly decreased the recurrence rate in VKH patients (P = 0.009).
CONCLUSION
In comparison to acute-resolved patients, chronic-recurrent patients exhibited poorer initial BCVA and a significantly increased incidence of "sunset glow fundus." Older age at onset and the occurrence of "sunset glow fundus" at diagnosis are crucial predictive factors for VKH patients progressing to the chronic recurrent phase. ADA effectively alleviates refractory VKH disease and is generally well-tolerated.
Topics: Humans; Uveomeningoencephalitic Syndrome; Adalimumab; Female; Male; Retrospective Studies; Adult; Middle Aged; Recurrence; Visual Acuity; Chronic Disease; Young Adult; Anti-Inflammatory Agents; Follow-Up Studies; Adolescent; Treatment Outcome; Aged; Prognosis
PubMed: 38849758
DOI: 10.1186/s12886-024-03511-9 -
Journal of Cutaneous Medicine and... Jun 2024There has been a call to action to enhance representation of non-white individuals in dermatology clinical trials. Investigations in differential response to treatment... (Review)
Review
There has been a call to action to enhance representation of non-white individuals in dermatology clinical trials. Investigations in differential response to treatment across populations are limited, particularly in conditions of commonality, impact, distinct presentation, and diagnosis in non-white participants, such as atopic dermatitis and psoriasis. This systematic review summarized and identified if biologic treatment outcomes in moderate-to-severe atopic dermatitis and psoriasis varied in skin of colour (SOC) participants in phase 3 trials. MEDLINE, COCHRANE, and EMBASE databases were used to conduct the search following PROSPERO registration. Following screening of 3209 articles, 11 studies were collected with 1781 SOC participants with a mean age of 40.99 ± 6.3 years (range: 30.6-51.6 years). Male participants accounted for 76.9% (n = 1370/1781) of the sample, and Chinese, Japanese, Taiwanese, and Korean participants accounted for 64.3%, 24.2%, 4.5%, and 3.4% of participants, respectively. Participants with atopic dermatitis were treated with dupilumab (n = 216/388) and participants with psoriasis were treated with adalimumab (n = 313/1393), bimekizumab (n = 62/1393), ixekizumab (n = 13/1393), secukinumab (n = 117/1393), and ustekinumab (n = 289/1393). No significant SOC population-based outcomes were found across treatment groups. However, differences in baseline characteristics or comorbidities were found, suggesting race or ethnic background should be considered when treatment is prescribed in psoriasis or atopic dermatitis. Although no significant SOC participant differential response to treatment were found, large-scale randomized controlled trials investigating comparable treatment outcomes and stratifying results by SOC population in atopic dermatitis and psoriasis are warranted to confirm these findings.
PubMed: 38847375
DOI: 10.1177/12034754241260023