The weight is off, the DMARDs are off - now what? Save

Sometimes it’s only when we have effective solutions that we have to think about what to do next. And when that happens, remember why we do things in the first place. In an era when weight loss is happening on scale, now we need to think about the goals after the weight is lost.

Weight loss seems more achievable now than it ever has been - partially because it is more achievable, but partially because now we believe that it is achievable. It isn’t a futile exercise that seems to create unnecessary tension in the therapeutic relationship. We’ve rethought our approach to be more proactive, and we now have not just medical, surgical, and structured lifestyle options, but now our patients believe it’s possible, too.

That promised land of substantive weight loss comes within it the illusion of better disease control and, for inflammatory arthritis patients, the possibility of reducing the burden of regular medicines - often driven by the patient, with or without telling you. It is a dream worth aspiring to and, as we’ve discussed this month, one which is increasingly achievable, albeit still for a small minority of patients.

So for those who do reach that ultimate goal, what next?

Most pragmatically, weight loss is not always forever. In fact, for the majority, it isn’t. The metabolic system fundamentally does want to defend its set point weight and it needs sustained change to hold against that tide. We know this from the days when lifestyle measures without sustained structure led to yo-yo dieting, but it has become even more clear when initial change is less willpower and more pharmacology. For many, GLP-1 therapy is unsustainable as an indefinite therapy, and if it is stopped altogether, it is clear that weight is gained again.

This doesn’t always mean that the inflammatory arthritis comes roaring back. Having said that, we have already seen this movie play out enough times in our clinical practice to know how it ends. Even if the return in symptoms with weight gain isn’t as reliable in inflammatory arthritis as it is in osteoarthritis or gout, it certainly happens a lot of the time, with appropriate disappointment. In fact, too often we end up in a worse situation: muscle is lost with weight loss but not regained with weight regain, and an understandable reluctance to get back on effective treatments for inflammatory arthritis can leave us with a more persistent version to deal with, for reasons mechanical, epigenetic, and nociplastic.

More interestingly, though, stopping a DMARD is not the end - in fact, not even the beginning of the end. Of course, there is the early mirage of drug-free remission in patients whose return of disease activity is on the way. If there is a natural tendency for patients to try and ignore those symptoms as they re-emerge, it falls upon the proactive rheumatologist to remain vigilant, even after the medications that typically necessitate such supervision have been discontinued.

Patients might live with less pain and more energy in the short term, with better sleep, mobility, mechanical loading, function, and indeed a better patient global assessment, and we should be delighted for them for it. Indeed, as we have seen discussed in Tuesday Night Rheumatology, systemic inflammation may well subside, and we hope for the flow-on consequences of that - not just lower inflammatory markers, but real and meaningful changes.

There is a serious risk, though, that synovitis and extra-articular inflammatory disease can persist even if they have improved. This isn’t a theoretical risk -  Veena Ranganath and colleagues from UCLA noted that, in a RCT of a weight loss intervention in obese RA patients, RAPID3, DAS28 and HAQ-DI all significantly improved in the intervention arm with its weight loss, but ultrasound changes did not. More subtle swelling and stiffness are easy to ignore, they also might not be obvious on a first pass, but just like DMARD tapering in any situation, vigilance is key - even if the hard-fought gains of weight loss are to be applauded. If that synovitis is there, it needs to be treated, just like in any other situation.

These patients need to be followed, even if they insist otherwise. When I haven’t insisted on this, I’ve regretted it. Although we don’t have the evidence for it now, GLP-1 receptor agonists may well turn out to be DMARDs of sorts themselves, but their success may not necessarily be complete, and they may not be the panacea for all of our problems.

If our mantra is “don’t stop the meds”, and we remain on high alert when they are stopped, the presence of weight loss leading to reduced inflammation shouldn’t change that.