August 31, 2026  ·  Weekly Newsletter

Good morning, Reader.

This week, the continued expansion of JAK inhibitors beyond ruxolitinib in myelofibrosis creates a new kind of complexity for clinicians. We are no longer debating efficacy in a vacuum; we are now choosing between multiple effective options, each with its own profile. That choice demands precision.

1. **JAK Inhibitor Proliferation**, Since ruxolitinib's 2011 approval, three more JAK inhibitors have entered the market for myelofibrosis, complicating treatment decisions. Clinicians must weigh subtle differences. 2. **Tolvaptan Efficacy in ADPKD**, Tolvaptan slows the increase in total kidney volume in autosomal dominant polycystic kidney disease, but direct translation to preserved function remains a question. Kidney growth is not the only metric. 3. **Gabapentinoid Doubt**, Gabapentinoids are widely prescribed for sciatica and radicular pain, but evidence suggests their efficacy is less robust than often assumed in clinical practice. Prescribing patterns persist.

The pattern emerging is one of refinement. New therapies are effective, but their integration into practice demands a deeper understanding of specific patient populations and precise endpoints beyond initial headline benefits. This is about optimising, not just treating.

Clinicians must now ask not just "does it work?", but "does it work better, for this patient, right now?" I read every reply.

Myelofibrosis

Myelofibrosis (MF) presents a chronic challenge, marked by myeloproliferation, bone marrow fibrosis, and debilitating splenomegaly and constitutional symptoms. The disease's hallmark, constitutive activation of JAK-STAT signaling, has driven the development of targeted therapies. Since ruxolitinib's 2011 approval, three additional JAK inhibitors have entered the market, complicating treatment decisions for clinicians. 1 These therapies are not curative; allogeneic stem cell transplantation…