Archive for month: February, 2024

A recent meta-analysis of randomized clinical trials did not identify a significant rise in the risk of VTE and MACE in dermatology patients receiving JAK-STATi for a median duration of 16 weeks.

The results of the review published in JAMA Dermatology suggest that the evidence is insufficient regarding an increased risk of cardiovascular complications conferred by JAK-STATi in dermatological patients, particularly when used for short time frames.

JAK-STATi include Janus kinase and tyrosine kinase 2 (TYK2) inhibitors, medications that target the JAK-STAT pathway; a series of intracellular mediators that result in amplification and gene transcription through a secondary messenger pathway. Over the past decade, JAK-STATi has revolutionized the management of several dermatological conditions.

In 2022, the ORAL study, a large open-label randomized clinical trial, suggested that rheumatoid arthritis patients receiving JAK-STATi may be at higher risk of MACE and VTE. This prompted a classwide black box warning counselling against their use in patients above 65 years or with preexisting cardiovascular risk factors. Similarly, dermatological guidelines have recommended against JAK-STATi use in certain population groups, or only in patients who have failed trials of more established therapies, including TNF inhibitors.

Against the above background, Patrick A. Ireland, Prince of Wales Hospital, Randwick, New South Wales, Australia, and colleagues aimed to evaluate the risk of VTE, MACE, serious adverse events (SAEs), and tolerability of systemic JAK-STATi compared with placebo, in those with a dermatologic indication.

For this purpose, the researchers carried out a systematic review of the literature from June 2023 using online databases. The analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.

The eligibility criteria of the studies were placebo-controlled randomized clinical trials that compared systemic JAK-STATi with placebo and investigated the safety in patients with atopic dermatitis, vitiligo, psoriasis, alopecia areata, lichen planus or hidradenitis suppurativa. Study selection and data extraction were carried out by two authors working independently using a standardized template.

The main outcomes were the incidence of VTE, SAE, MACE, and study discontinuation due to TEAEs. Analysis of these values was done against person exposure years to determine the incidence rate (IR). Risk ratios (RRs) compared incidence rates among treatment and placebo comparator arms.

The researchers reported the following findings:

• Forty-five randomized clinical trials were eligible for inclusion, with 12 996 patients receiving active JAK-STATi therapy and 4925 allocated to placebo treatment.
• There was no significant increase in MACE (I2 = 0.00%; RR, 0.47) or VTE (I2 = 0.00%; RR, 0.46) between placebo and JAK-STATi comparator arms.
• There was also no significant difference in SAEs (I2 = 12.38%; RR, 0.92) and discontinuations between JAK-STATi and placebo (I2 = 23.55%; RR, 0.94).

“We did not identify a significant increase in the risk of MACE and VTE in dermatology patients receiving JAK-STATi in the short term,” the researchers wrote.

The results aid in reassuring clinicians that prescribing these medications in short intervals to patients with low CV risk profiles appears to be both well tolerated and safe in this cohort.

“Given the limited evidence, clinicians must remain judicious in their use of these medications for long durations and in high-risk patient populations,” the research team concluded.

Reference:

Ireland PA, Jansson N, Spencer SKR, Braden J, Sebaratnam D. Short-Term Cardiovascular Complications in Dermatology Patients Receiving JAK-STAT Inhibitors: A Meta-Analysis of Randomized Clinical Trials. JAMA Dermatol. Published online January 31, 2024. doi:10.1001/jamadermatol.2023.5509

New Delhi: The District Consumer Disputes Redressal Commission directed Oriental Insurance Company to reimburse a medical claim amount of more than Rs 1.88 lakh along with a compensation of Rs 7,500 for deficiency in services to a policyholder.

The direction of the District Consumer Disputes Redressal Commission (East Delhi) came on the man’s complaint that the amount was not paid to him despite submitting a claim of Rs 1,88,729 along with requisite documents to Oriental Insurance Company Ltd in 2017.

The commission, comprising President S S Malhotra and Members Rashmi Bansal and Ravi Kumar, in a recent order, noted that the complainant’s wife was taking treatment at AIIMS and the raised claim was not disputed by the insurer.

It rejected the company’s arguments that the complainant did not submit the requisite documents.

“Fact otherwise is well proved that the complainant has filed all the necessary documents along with the complaint and exhibited all the documents. Therefore, it appears to the commission, that the contention that the complainant did not cooperate or did not furnish the document/details appears to be an afterthought,” the commission said.

Stating that not reimbursing the claim amounted to deficiency in services, the commission directed Oriental Insurance to pay the amount with interest along with Rs 7,500 as compensation and Rs 5,000 as litigation costs.

Medical Dialogues team had earlier reported that the Madurai bench of Madras High Court reiterated that a claim for medical reimbursement cannot be rejected merely because the treatment was undertaken in a non-networking hospital. “The issues regarding the settlement of the medical claim are no more res-integra in respect of the treatment undertaken in a non-network hospital. Several orders have been passed by the Courts to settle the medical reimbursement claim and not to reject the same merely on the ground that the hospital is not falling under the list of network hospitals,” noted the HC bench comprising Justices SM Subramaniam and V Lakshminarayanan. 

Diabetic foot ulcer (DFU) is a disabling complication of diabetes mellitus. Here, we attempted to assess whether long-term intrafemoral artery infusion of low-dose urokinase therapy improved Diabetic foot ulcers and decreased cardiovascular events in patients with Diabetic foot ulcers. Diabetic foot ulcers were randomized to continuous intrafemoral thrombolysis or conventional therapy groups. The continuous intrafemoral thrombolysis group received continuous intrafemoral urokinase injection for 7 days, and conventional therapy just received wound debridement and dressing change. Then, a follow-up of average 6.5 years was performed. Results: Compared with conventional therapy, at the first 1 month of intervention stage, the ulcers achieved a significant improvement in continuous intrafemoral thrombolysis group including a complete closure (72.4% vs 17.5%), an improved ulcer (27.6% vs 25.8%), unchanged or impaired ulcer (0% vs 56.7%). During the 6.5-year follow-up, for the primary outcome of ulcer closure rate, continuous intrafemoral thrombolysis therapy obtained a better complete healing rate. For the secondary outcome of cardiovascular disease events, continuous intrafemoral thrombolysis therapy had a lower incidence of cardiovascular events. Importantly, intrafemoral thrombolysis therapy decreased the incidence of cardiovascular death (HR 0.42 Additionally, continuous intrafemoral thrombolysis therapy improved local skin oxygenation, peripheral neuropathy, and glycolipid metabolic profiles compared to conventional therapy group (p<0.05). Continuous intrafemoral thrombolysis therapy has a better therapeutic efficacy to improve Diabetic foot ulcers and decrease cardiovascular events.

Reference:

Tong J, Zhang J, Xiang L, Li S, Xu J, Zhu G, Dong J, Cheng Y, Ren H, Liu M, Yue L, Xiang G. Continuous intrafemoral artery infusion of urokinase improves diabetic foot ulcers healing and decreases cardiovascular events in a long-term follow-up study. BMJ Open Diabetes Res Care. 2024 Jan 12;12(1):e003414. doi: 10.1136/bmjdrc-2023-003414. PMID: 38216296.

Urokinase therapy, diabetic foot ulcers, diabetes and CV, diabetes patients, BMJ Open Diabetes Research & Care, Tong J, Zhang J, Xiang L, Li S, Xu J, Zhu G, Dong J, Cheng Y, Ren H, Liu M, Yue L, Xiang G, diabetic foot