Pharmacology Concepts by Dr Mahtab Khan

23/06/2022

Oxidative phosphorylation

26/03/2022

26/03/2022

News:
FDA Approves Upadacitinib for Moderately to Severely Active Ulcerative Colitis

Patients treated with upadacitinib achieved clinical remission of ulcerative colitis more frequently through weeks 8 and 52 versus the placebo group.

The FDA has approved upadacitinib (Rinvoq; AbbVie) for the treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to 1 or more tumor necrosis factor (TNF) blockers.

The action represents the first approval for upadacitinib in the field of gastroenterology. The approval was based on 3 randomized, double-blind, placebo-controlled phase 3 clinical trials. These included the U-ACHIEVE and U-ACCOMPLISH induction studies, in which upadacitinib was evaluated at 45 mg once daily for 8 weeks, followed by 15 mg or 30 mg once daily in the maintenance trial for 52 weeks.

The investigators found that patients treated with upadacitinib achieved clinical remission more frequently through weeks 8 and 52 versus the placebo group. The primary endpoint of the study was stool frequency subscore (SFS) ≤ 1 and not greater than baseline, re**al bleeding subscore (RBS) = 0, and endoscopy subscore (ES) of ≤ 1 without friability.

During the U-ACHIEVE and U-ACCOMPLISH induction trials at week 8, 26% and 33% of patients treated with upadacitinib 45 mg achieved clinical remission compared to 5% and 4% of patients administered placebo. Onset of response was observed as early as week 2, with a greater proportion of patients administered upadacitinib 45 mg once daily achieving clinical response, defined as a decrease of ≥1 point and ≥30 percent from baseline and a reduction in RBS of ≥1 or an absolute RBS ≤1 per the pmMS, compared to placebo.

Further, upadacitinib achieved all ranked secondary endpoints, including endoscopic improvement and histologic-endoscopic mucosal improvement, as well as corticosteroid-free clinical remission.

During the maintenance trial, 42% and 52% of patients administered upadacitinib 15 mg or 30 mg, respectively, achieved clinical remission at week 52 versus 12% of patients in the placebo group.

The study also found that 57% and 68% of patients administered upadacitinib 15 mg or 30 mg, respectively, achieved corticosteroid-free remission, defined as clinical remission (per mMS) and corticosteroid-free for ≥90 days immediately preceding week 52 in patients who achieved clinical remission at the end of the induction treatment, versus 22% of patients on placebo.

"Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding," said Maria T. Abreu, MD, Professor of Medicine, Professor of Microbiology and Immunology, University of Miami Miller School of Medicine and Director, Crohn's & Colitis Center, University of Miami Health System, in a press release. "In clinical trials, upadacitinib showed its ability to control symptoms for many patients."

Reference

RINVOQ® (upadacitinib) Receives FDA Approval for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis. AbbVie. [news release]. March 16, 2022.

March 16, 2022 RINVOQ® (upadacitinib) Receives FDA Approval for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis In clinical trials, RINVOQ (upadacitinib) achieved the primary endpoints of clinical remission (per modified Mayo Score [mMS]) at weeks 8 and 521-4  A great...

22/02/2022

Antidote for Iron

18/01/2022

WHO Recommends 2 New Drugs to Treat Patients With COVID-19
January 18, 2022
Ashley Gallagher, Assistant Editor
The World Health Organization issues a strong recommendation for baricitinib and a conditional one for sotrovimab.

A World Health Organization (WHO) group has issued a strong recommendation for the use of baricitinib to treat patients with COVID-19 and a conditional recommendation for the use of sotrovimab to treat the disease.

Baricitinib, a type of Janus kinase (JAK) inhibitor, is used to treat rheumatoid arthritis, but can also treat individuals with critical or severe COVID-19 in combination with corticosteroids, according to a WHO Guideline Development Group of International experts and published in The BMJ.

Their recommendation is based on moderate certainty evidence that baricitinib improves survival and reduces the need for ventilation, with no observed increase in adverse effects.

The WHO experts said that baricitinib has similar effects to other arthritis drugs called interleukin-6 (IL-6) inhibitors, so when both are available, they recommend choosing a treatment based on availability, clinician experience, and cost.

Using both drugs at the same time is not recommended.

The experts advise against the use of 2 other JAK inhibitors, ruxolitinib and tofacitinib, for individuals with critical or severe COVID-19, because low certainty evidence from small trials failed to show a benefit and suggests a possible increase in serious adverse effects with tofacitinib.

In the same guidelines update, the WHO experts also conditionally recommended the use of the monoclonal antibody sotrovimab for individuals with non-severe COVID-19 but only those who are at highest risk of hospitalization, reflecting trivial benefits in those at lower risks.

The WHO experts made a similar recommendation for casirivimab-imdevimab, another monoclonal antibody drug.

There is insufficient data to recommend 1 monoclonal antibody treatment over another, and the WHO experts acknowledged that their effectiveness against new variants, such as omicron, is still uncertain.

The guidelines for monoclonal antibodies will be updated when additional data become available, the WHO experts said.

The new recommendations are based on new evidence from 7 trials that include 4000 individuals with critical, non-severe, and severe COVID-19 infection.

These recommendations are part of a living guideline, developed by WHO and the methodical support of MAGIC Evidence Ecosystem Foundation, to provide guidance on the management of COVID-19 and help physicians make better decisions for patients.

Living guidelines are useful in fast-moving research areas, such as COVID-19, because they allow investigators to update previously peer-reviewed and vetted evidence summaries as new information becomes available.

The panel considers a combination of evidence assessing relative benefits, feasibility, harm, preferences, and values to make their recommendations.

The new guidance adds to previous recommendations for the use of conditional recommendations for the use of casirivimab-imdevimab, another monoclonal antibody treatment, in selected individuals; IL-6 receptor blockers and systemic corticosteroids for individuals with critical or severe COVID-19; and against the use of convalescent plasma, hydroxychloroquine, or ivermectin in individuals with COVID-19, regardless of disease severity.

Reference

WHO recommends two new drugs to treat patients with COVID-19. EurekAlert. News release. January 13, 2022. Accessed January 14, 2022.

The drug baricitinib (a type of drug known as a Janus kinase (JAK) inhibitor, also used to treat rheumatoid arthritis) is strongly recommended for patients with severe or critical covid-19 in combination with corticosteroids, says a WHO Guideline Development Group of international experts in The BMJ...

03/01/2022

Information

23/12/2021

Rosuvastatin:

Indication: Rosuvastatin is used as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, non-HDL-C, and TG levels and to increase HDL-C for patients with primary hyperlipidemia and mixed dyslipidemia.

03/08/2021

100 softwares for students

30/05/2021

Histoacryl:
Histoacryl glue is used increasingly for the treatment of gastric and ectopic varices, and there is experience in its use for oesophageal varices. It is an effective treatment, yet numerous reports of complications have accumulated. This review of the literature describes the technique, explores circulatory and vascular consideration unique to portal hypertension and categorises the complications into: “Embolisation”, “local venous thrombosis”, “fistulisation and extravascular injection”, “ulceration, erosion and extrusion”, and “nidus of infection”. A case is then made for standardisation of the technique and the consent process.
Ref:

Histoacryl glue is used increasingly for the treatment of gastric and ectopic varices, and there is experience in its use for oesophageal varices. It is an effective treatment, yet numerous reports of complications have accumulated. This review of the ...

04/05/2021

What's the difference between Passion and Vision?

10/04/2021

https://youtu.be/L_0WQZv7BQE

27/03/2021

"Septicemia" may suppress "temperature- thermostat" in our body, and ultimately no fever is recorded inspite of severe infection.