MSD Pharma gets CDSCO panel nod for New Indications of Pembrolizumab in India

New Delhi: The Subject Expert Committee functioning under the Central Drugs Standard Control Organization (CDSCO) has granted approval for additional indications of Pembrolizumab (Keytruda) Injection 100 mg/4 ml, manufactured by MSD Pharmaceuticals, expanding its use for advanced cancers in India. However, the nod came with a condition that the firm should conduct a Phase IV study in India in these indications.

The recommendation was made after the drug maker MSD Pharmaceuticals presented the proposal for the grant of approval of the following additional indications of the drug Pembrolizumab Injection 100 mg/mL based on the safety and efficacy data generated from global clinical trials in these indications, along with the request for a local clinical trial waiver.

i. KEYTRUDA (pembrolizumab) in combination with chemoradiotherapy (external beam radiation therapy followed by brachytherapy), is indicated for the treatment of FIGO 2014 Stage III – IVA locally advanced cervical cancer in adults who have not received prior definitive therapy.

ii. KEYTRUDA (pembrolizumab), in combination with fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumors express PD-L1 with a CPS≥1.

iii. KEYTRUDA® (pembrolizumab), in combination with gemcitabine and cisplatin, is indicated for the first-line treatment of locally advanced unresectable or metastatic biliary tract carcinoma in adults.

Pembrolizumab is a PD-1 blocking antibody used to treat various types of cancer, including metastatic melanoma, non-small-cell lung cancer, cervical cancer, head and neck cancer, and Hodgkin’s lymphoma.

Pembrolizumab binds with high affinity to the cell surface receptor programmed cell death protein 1 (PD-1) and antagonizes its interaction with its known ligands PD-L1 and PD-L2. Under normal circumstances, the binding of the ligands of PD-1 to the receptor inhibits the TCR-mediated T-cell proliferation and cytokine production. This inhibitory signal appears to play a role in self-tolerance and collateral damage minimization after immune responses against a pathogen and maternal tolerance to fetal tissue.

Also Read:Intas Pharma Told to Narrow Margins, Extend Duration in Pembrolizumab Trial Protocol

The binding of pembrolizumab to PD-1 prevents this inhibitory pathway, causing a physiological shift towards immune reactivity and enhancing tumor immunosurveillance and anti-tumor immune response.

At the recent SEC meeting for Oncology, the expert panel reviewed the proposal presented by MSD Pharmaceuticals for additional indications of Pembrolizumab (Keytruda) Injection 100 mg/4 ml.

The committee noted that the proposed indications are approved in major countries, including the USA, the EU, the UK, Japan, and Australia.

The committee further noted, “There is no clinical data available in Indian patients for these indications; however, the firm has generated safety data in a Phase IV study conducted in India in other indications.”

After detailed deliberation, the committee recommended approval of the proposed additional indications with a condition to conduct a Phase IV study in India in these indications.

Accordingly, the expert panel suggested that the firm should submit the Phase IV study protocol within three months of approval of the additional indication.

Also Read: Padcev plus Keytruda significantly improves survival for certain patients with bladder cancer when given before, after surgery: Pfizer

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Nocturnal Blood Pressure Dips Linked to Rapid Central Vision Loss in Normal-Tension Glaucoma: Study

Korea: Patients with normal-tension glaucoma (NTG) who experience pronounced drops in nocturnal blood pressure are at a significantly higher risk of rapid central visual field loss, a new study published in the American Journal of Ophthalmology has shown. 

The research found that over half of NTG patients classified as “over-dippers” exhibited fast central visual field progression, emphasizing the need for careful monitoring in this high-risk group.
The study was led by Dr. Jimin Park from the Department of Ophthalmology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, along with a team of colleagues. The investigators aimed to explore the link between nocturnal blood pressure fluctuations and the rate of central visual field deterioration in patients with early-to-moderate NTG, a common subtype of glaucoma characterized by optic nerve damage despite normal intraocular pressure.
In this prospective cohort study, 199 untreated NTG patients underwent 24-hour ambulatory blood pressure monitoring (ABPM) in their usual daily settings and were followed for a minimum of two years, with an average follow-up of 4.9 years. Based on their nighttime blood pressure patterns, participants were categorized as non-dippers, dippers, or over-dippers. Central visual field progression was measured using the mean total deviation of the 12 central points (MTD10), with “fast progression” defined as a decline of more than 0.5 dB per year.
The study led to the following findings:
  • Over-dippers showed a mean MTD10 decline of -0.53 dB/year, faster than dippers (-0.27 dB/year) and non-dippers (-0.23 dB/year).
  • 60% of over-dippers experienced fast central visual field progression.
  • 23.5% of dippers and 19.8% of non-dippers experienced fast central visual field progression.
  • The percentage of nocturnal mean arterial pressure (MAP) dip was identified as a significant predictor of rapid central visual field loss, with an odds ratio of 1.062.
These findings highlight a crucial clinical insight: pronounced nocturnal blood pressure dips can accelerate central visual field deterioration in NTG patients. Central vision is vital for daily tasks such as reading and recognizing faces, and rapid loss in this area can substantially impair quality of life. The study suggests that ophthalmologists should closely monitor NTG patients exhibiting significant nocturnal BP reductions and consider integrated management strategies that address both ocular and systemic cardiovascular factors.
While the study provides valuable evidence linking blood pressure patterns to glaucoma progression, the authors note that further research is needed to determine whether interventions to stabilize nocturnal blood pressure can slow visual field loss. Nevertheless, the current findings underscore the importance of personalized care in NTG, particularly for patients at risk of rapid central visual field decline.
Dr. Park and colleagues’ research demonstrates that over-dipping during sleep is a key risk factor for accelerated central visual field loss in NTG, affecting more than half of these patients. Early identification and vigilant monitoring of at-risk individuals could play a critical role in preserving central vision and preventing functional impairment in glaucoma patients.
Reference:
Park, J., Song, W. K., Yoon, J., Kim, K. E., & Kook, M. S. (2025). Fast Central Visual Field Progression in Patients with Normal-Tension Glaucoma and Nocturnal Blood Pressure Dip. American Journal of Ophthalmology. https://doi.org/10.1016/j.ajo.2025.09.018

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Previous use of LNG-IUS associated with decreased endometrial growth in women undergoing IVF/ICSI: Study

Long-acting reversible contraceptive methods are among the
most effective contraceptives available today and are an advantageous choice of
contraception for women who wish to conceive in the future. Among these is the
levonorgestrel intrauterine system (LNG-IUS), the use of which has increased in
recent years. The LNG-IUS releases levonorgestrel locally, causing the cervical
mucus to thicken, thereby decreasing spermatozoa motility, which creates a
hostile environment for the spermatozoa. Further, it causes atrophy of the
endometrium. The combination of these effects prevents fertilisation and
implantation. As LNG-IUS is a reversible contraceptive method, removal should
result in a return to baseline fertility. However, current literature on this
topic is contradicting. While some studies have shown that the use of LNG-IUS
does not affect the return to baseline/ normal fertility after removal, others
have found delayed conception after removal. Endometrial development plays an
essential role in achieving pregnancy, as a sufficient endometrial thickness
(EMT) is needed for successful embryonic implantation into the uterine wall. A
previous study investigated the effect of combined oral contraceptive pill
(OCP) use on the endometrium and found that long-term use of OCPs may have a
negative effect on endometrial growth.

As OCPs and LNG-IUSs are both hormonal contraceptive methods
containing progestin, it can be hypothesised that the use of LNG-IUS may also
affect endometrial growth and thereby fertility. Consequently, the objective of
this study was to investigate whether previous use of the LNG-IUS negatively
influences the EMT in women undergoing in vitro fertilisation
(IVF)/intracytoplasmic sperm injection (ICSI) treatment.

This study was a register-based multicentre historical
cohort study. The study has been reported in accordance with Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE).

It was a Multicentre historical cohort study from eight
Danish public and private fertility clinics. 12786 women aged 18–46 years
contributing with an EMT measurement from 22464 different IVF/ICSI treatment
cycles between 2000 and 2021 were taken. Exposure was previous use of LNG-IUS,
combined oral contraceptive pills (OCPs), progesterone -only pills (POPs), no/
other contraception or combined, cumulated use of contraception when more
contraceptives had been used during the inclusion period. Further, ever use of
LNG-IUS was categorised into 0–3 years, > 3–6 years, > 6–9 years and
>9 years. Mixed effect logistic regression adjusted for age, BMI, smoking,
educational level, total FSH dose and fertility clinic was used.

Statistically significantly higher odds of EMT ≥7mm were
found for OCPs [odds ratio (OR) 3.53 (95% confidence interval (95% CI)
1.29–9.65)], POPs [OR 6.43, (95% CI 1.45–28.63)] and no/other contraception [OR
6.67, (95% CI 2.37–18.74]) relative to LNG-IUS in IVF/ICSI cycles. Further, all
duration categories of ever use of LNG-IUS were associated with statistically
significantly lower odds of obtaining an EMT ≥7mm compared to no/other
contraception.

In this study, previous use of LNG-IUS was associated with
statistically significantly lower odds of obtaining an EMT ≥7mm when compared
to other contraceptive methods in IVF/ICSI cycles. Further, authors found a
statistically significant association between ever use of LNG-IUS and a thin
endometrium compared to no/other previous use of contraceptives regardless of
the duration of use.

In conclusion, this study showed that previous use of
LNG-IUS might have a negative impact on the EMT in IVF/ICSI cycles. However,
authors acknowledge that this present study has limitations, which should be
considered when interpreting the results. Future research should accommodate
these limitations to create evidence-based knowledge on the potential prolonged
negative impact of LNG-IUS on the endometrium and its receptivity in IVF/ICSI
cycles.

Source: Mette Peters Michaelsen;
Laura Cæcilie Nielsen; Michelle Poulsen; BJOG: An International
Journal of Obstetrics & Gynaecology, 2025; 0:1–8
https://doi.org/10.1111/1471-0528.18295

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TAVR Outcomes in ESRD Patients Remain Poor, Large Study Shows

USA: Patients with end-stage renal disease (ESRD) who undergo transcatheter aortic valve replacement (TAVR) continue to face significantly worse outcomes compared to those without kidney failure, and these risks are not reduced even when treated at high-volume centers, according to a study published in The Annals of Thoracic Surgery.

The research was conducted by Dr. Esteban Aguayo and colleagues from the Department of Surgery, David Geffen School of Medicine, UCLA, who evaluated national outcomes of TAVR among patients with ESRD. Although TAVR is widely regarded as a less invasive and safer alternative to surgical aortic valve replacement in the general population, the study highlights that patients with severe kidney disease remain at heightened risk of mortality, prolonged hospitalizations, and frequent readmissions.
Using data from the National Readmissions Database between 2016 and 2021, the investigators analyzed more than 411,000 adult patients who underwent TAVR. Of these, approximately 7.3 percent were identified as having ESRD. Patients were grouped according to their renal status, and outcomes such as in-hospital mortality, 30-day readmission, length of hospital stay, procedural complications, and hospitalization costs were assessed. The study also examined whether institutional experience, defined by procedural volume, influenced these outcomes by comparing low-volume hospitals with high-volume centers.
The findings revealed the following:
  • ESRD was linked to a 79% higher likelihood of in-hospital death compared with non-ESRD patients.
  • The risk of 30-day readmission was 87% greater in ESRD patients.
  • ESRD patients stayed in the hospital 1.3 days longer on average.
  • Hospitalization costs for ESRD patients were about $1,000 higher.
  • Non-ESRD patients benefited from lower mortality and readmission risks when treated at high-volume hospitals.
  • This protective effect of high-volume centers was not observed in ESRD patients.
  • Patients with ESRD continued to face persistently high rates of mortality and readmissions regardless of hospital volume.
The authors emphasized that these findings highlight the importance of individualized decision-making when considering TAVR in patients with ESRD. While the procedure may offer symptom relief and an alternative to open-heart surgery, its benefits are limited by the elevated risks inherent in this population. The study suggests that optimal patient selection, thorough pre-procedural evaluation, and strategies aimed at minimizing complications are essential to improving outcomes.
Dr. Aguayo and his team concluded that ESRD patients undergoing TAVR represent a particularly vulnerable group, and that high procedural volumes alone are insufficient to overcome their adverse prognosis. The research calls for more focused efforts to refine risk stratification and develop tailored management approaches to address the challenges of performing TAVR in patients with advanced kidney disease.
Reference:
Aguayo E, Kwon OJ, Won M, Mallick S, Coaston T, Vadlakonda A, Tabibian K, Sanaiha Y, Shemin RJ, Benharash P, Impact of Transcatheter Aortic Valve Replacement Volume on Outcomes in Patients with End Stage Renal Disease, The Annals of Thoracic Surgery (2025), doi: https://doi.org/10.1016/j.athoracsur.2025.08.009.

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Chronic Sinus Inflammation Linked to Increased Risk of Rheumatoid Arthritis: Study

A new systematic review and meta-analysis published in the International Forum of Allergy & Rhinology revealed a striking connection between rhinosinusitis, and the development of systemic rheumatic diseases. The findings suggest that chronic sinus inflammation may not only affect breathing and quality of life but could also unmask hidden autoimmune conditions.

This study included data from 9 international studies and examined whether individuals with rhinosinusitis face higher odds of developing conditions like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis. By analyzing both prevalence and risk, this study applied random-effects models to ensure statistical robustness.

The results revealed a strong association between chronic rhinosinusitis (CRS) and systemic rheumatic conditions. The patients with CRS were nearly twice as likely to develop rheumatoid arthritis (odds ratio [OR]: 1.70, 95% confidence interval [CI]: 1.44–2.00, p < 0.00001). Similarly, CRS carried a 61% higher risk of systemic lupus erythematosus (OR: 1.61, 95% CI: 1.25–2.08, p = 0.0002) and a 48% higher risk of ankylosing spondylitis (OR: 1.48, 95% CI: 1.26–1.72, p < 0.00001).

Acute rhinosinusitis (ARS) which is usually triggered by infections, showed weaker links, most notably to seronegative rheumatoid arthritis. This distinction highlight the role of chronic inflammation and long-term immune dysregulation in systemic autoimmunity.

The prevalence rates showed rheumatoid arthritis to emerge as the most frequent autoimmune diagnosis among rhinosinusitis patients, affecting about 10% (95% CI: 8.2–13). This prevalence significantly exceeds baseline rates in the general population, suggesting that sinus-related inflammation could be an early sentinel for autoimmune disease.

Overall, the findings highlight a mucosal immune dysfunction in rhinosinusitis may act as a trigger or parallel pathway in the development of systemic autoimmune conditions. For patients with CRS, particularly those unresponsive to conventional therapies, rheumatologic evaluation could be warranted. Early detection of autoimmune conditions can dramatically improve outcomes through timely intervention.

While more longitudinal studies are needed, the evidence suggests that chronic rhinosinusitis is more than a localized ENT disorder. It may serve as an early warning sign of systemic rheumatic disease, which could urge clinicians to adopt a more integrative approach when treating sinus patients.

Source:

Aulakh, A., Choudhary, P., Sidhu, G., Gigliotti, D., Jun, J., & Thamboo, A. (2025). The risk of rheumatic disorders among patients with rhinosinusitis: A systematic review and meta-analysis. International Forum of Allergy & Rhinology, alr.70032. https://doi.org/10.1002/alr.70032

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Intralesional Triamcinolone Outperforms Methotrexate in Alopecia Areata, suggests research

A new clinical study published in the Journal of Cosmetic Dermatology revealed in a head-to-head trial that intralesional triamcinolone led to significantly greater hair regrowth and patient satisfaction when compared to methotrexate in localized alopecia areata (AA) treatment.

Alopecia areata affects millions worldwide, manifesting as sudden hair loss in small patches or, in severe cases, across the entire scalp. Corticosteroid injections, particularly with triamcinolone acetonide (TrA), are often the frontline treatment, while methotrexate (MTX), which is a drug with immune-suppressing properties, has been investigated as an alternative. However, few studies have directly compared their effectiveness.

In this trial, a total of 40 patients with localized AA were divided into a group receiving monthly TrA injections and the other group given MTX over a 3-month period. Their progress was evaluated for 6 months using the Severity of Alopecia Tool (SALT), along with trichoscopic imaging, side effect tracking, and patient satisfaction scores.

The patients who received TrA injections showed an average 54.36% improvement in SALT scores, which indicated significant hair regrowth. The individuals on MTX experienced an average 54.6% worsening in scores, which suggests further hair loss rather than recovery.

The trichoscopic findings of both groups showed some changes. However, the only statistically meaningful result was a reduction in black dots, a marker of active hair follicle damage, seen in the MTX group. Despite this, the broader clinical outcomes still leaned heavily in favor of TrA.

The patients occasionally reported mild redness or pigmentation changes at injection sites, but no severe complications emerged. Also, satisfaction levels differed sharply, where the patients rated their experience with TrA an average 7.1 out of 10, when compared to just 4.9 for MTX.

The research found that TrA remains the superior choice for localized AA, both in regrowth effectiveness and patient experience. While MTX demonstrated some biological activity under the microscope, its inconsistent and often negative clinical impact makes it unsuitable as a frontline therapy at this stage.

Overall, the findings noted that further studies could explore whether methotrexate might perform better in adjusted doses or as part of combination regimens, potentially broadening treatment options for patients resistant to steroids.

Source:

Ghandi, N., Rashidi, A., Saberi, F., Abedini, R., Tootoonchi, N., & Babaie, H. (2025). Is intralesional methotrexate an effective alternative to intralesional triamcinolone in alopecia areata? Findings from a randomized controlled trial. Journal of Cosmetic Dermatology, 24(8), e70367. https://doi.org/10.1111/jocd.70367

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Cough Syrup Row: Rajasthan Practitioners Shift to Levocloperastine, Ambroxol Amid Dextromethorphan Concerns

New Delhi: Amid rising caution over the use of the widely prescribed cough suppressant dextromethorphan, medical practitioners and pharmacies in Sri Ganganagar, Rajasthan are increasingly switching patients to alternative medicines.

According to local reports, several clinics and chemists have started recommending substitutes such as levocloperastine, ambroxol, bromhexine, cetirizine + phenylephrine combinations, and herbal syrups in place of dextromethorphan. These options are being offered particularly in cases where patients are unable to tolerate the cough suppressant or where its use is considered unsafe.

Also Read: Probe Launched Against Rajasthan Pharma Firm Over Dextromethorphan Syrup-Linked Death

Among the alternatives, levocloperastine has emerged as a preferred choice due to its milder side-effect profile. Ambroxol and bromhexine, both mucolytics, are being prescribed where a productive cough needs thinning of mucus. Meanwhile, combinations of antihistamines and decongestants like cetirizine and phenylephrine are being used for patients with associated nasal congestion and postnasal drip. For those seeking gentler remedies, herbal syrups with soothing properties are being positioned as natural solutions.

Clinicians note that the shift away from dextromethorphan stems from its risk of misuse and potential adverse effects on the central nervous system. As a result, many prefer to prescribe agents that not only manage cough symptoms but also contribute additional therapeutic benefits such as mucus clearance or allergy relief.

Medical literature supports these practices, with levocloperastine recognised as a non-opioid antitussive with fewer sedative effects, and ambroxol/bromhexine established as standard expectorants in respiratory care. The substitution trend reflects a cautious, patient-centric approach by healthcare providers in the region, reports Dainik Bhaskar.

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Whooping cough can be fatal in young infants, experts warn

Pertussis, or whooping cough, is on the rise and incidence now exceeds pre-pandemic numbers. While in adults and older children the cough can be bothersome and last for months, pertussis in young infants can be life-threatening. Most children under 2 months of age with pertussis in the United States are hospitalized.

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Early medical abortion at home up to 12 weeks found to be safe, effective, comparable to hospital care

Early medical abortion at home up to 12 weeks of pregnancy is safe, effective, and comparable to hospital care, finds a five-year review of cases in Scotland, where this timeframe is legally permitted. The review was published online in the journal BMJ Sexual & Reproductive Health.

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Countries with highest reported levels of hearing loss also have lowest use of hearing aids, research finds

Countries with the highest reported levels of hearing loss also have the lowest reported use of hearing aids, finds international research published in the open access journal BMJ Global Health.

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