A supply gap is a pharmacological event
One omitted dose is a labelling question. Four omitted doses is a clinical one. The two are routinely conflated.
Maintenance
Page 4 of 9 of this archive, newest first.
The supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.
The eighteenth month, and the conversation that should have happened in the third
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
The steps get smaller as the ladder gets higher, and that is deliberate
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Escalating onto a rising curve
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Two-thirds back: the extension nobody expected to be the headline
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
The arithmetic of a step: what doubling a dose actually asks of you
The four-week step exists because four to five weeks is approximately how long a once-weekly drug takes to stop rising at a fixed dose. That is a good reason, and it is not…
The eighteenth month, and the conversation that should have happened in the third
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
Escalating onto a rising curve
The four-week step exists because four to five weeks is approximately how long a once-weekly drug takes to stop rising at a fixed dose. That is a good reason, and it is not…
Holding a dose is a decision, not a failure
Every major phase 3 protocol in this class allowed escalation to be delayed for tolerability. Almost no product label explains the mechanics of doing so.
A year after stopping: what the trials found at the far end
Fat mass, lean mass, and the composition of regained weight — the thinnest literature in this piece.
The lowest effective dose is a real concept with almost no data behind it
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
What the trial protocols permitted, and what the labels omitted
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.
Escalating onto a rising curve
We work the arithmetic out in full, because it is arithmetic and it is short.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
Three weeks off is a fresh start, whether or not you want one
Concentrations fall by half a week, so a month away leaves a small fraction of steady state. Resuming at the previous dose presents the receptor with a step it has not seen…
What a month without the drug does to tolerability
Concentrations fall by half a week, so a month away leaves a small fraction of steady state. Resuming at the previous dose presents the receptor with a step it has not seen…
The steps get smaller as the ladder gets higher, and that is deliberate
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
What STEP 8 tells us about maintenance, and what it does not
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
A design note on withdrawal trials, and why the run-in matters
The regain trajectories, arm by arm, with the estimands named.