Monday, 25 Mar 2019

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Managing Comorbidity and Poor Drug Responses

Comorbidity is pervasive and complicates medical care in general. It can be a by-product of aging. It may result from drug therapy or an inciting disease process and may be part of the constellation that defines the primary disorder.

Rheumatoid arthritis (RA) is one of many inflammatory disorders that carry a high risk of comorbidity. Most studies show that more than half of all RA patients have 1 or more comorbidities and that more than 25% have 2 or more comorbidities. Data from the Canadian CATCH cohort shows that even in early inflammatory arthritis (n=2090), at least one comorbid condition was reported by 76% of patients and comorbidities were  associated with higher disease activity, worse functional status and greater pain scores during the first year of care (http://bit.ly/2OH8Gcd)

The elderly are often undertreated and are less likely to receive DMARDs, TNF inhibitors or biologics.  Comorbidity and age significantly deters the use of aggressive therapies, including biologics. Hence comorbities, which tend to accumulate with age, can also deter the use of effective therapy. (http://bit.ly/2MSrZPz)

For many, it appears that inflammation and time (chronicity) yields a significant morbidity and comorbidity risk.  Furthermore, comorbidity on top of an inflammatory disorder (e.g., RA) uniformly leads to worse outcomes.

Moreover, there is a growing body of evidence that suggests that comorbidity has a significant dampening effect on drug responsiveness and, as stated above, adds to poorer outcomes in patients with inflammatory arthritis.

The problem is that most specialists do not engage in comorbidity care, as they assume that this is best done by the patient’s primary care physician. Unfortunately, patients with chronic inflammatory diseases tend to see their specialist and not their primary care physician for most of their medical needs.

Obesity.  Obesity is not only a risk factor for developing RA, Psoriasis and PsA; it has consistently been shown to impair therapeutic responses to both DMARD and biologic therapy. This is not a volume distribution issue as patients who are dosed according to weight (e.g., infliximab, tocilizumab) have the same issue regardless of BMI elevation. Some have speculated that this is related to proinflammatory adipokines or hormonal changes or even microbiome differences. Nonetheless, obesity (a common cofactor in comorbidity and the metabolic syndrome) places the patient at a significant therapeutic disadvantage.

Strober et al. studied TNF inhibitor (TNFi) persistence in 188 psoriatic arthritis patients (PsA) and found that female and those with metabolic syndrome-related co-morbidities have lower persistence on a TNFi. (http://bit.ly/2MeKKAp

Data from the Danish and Icelandic registries (DANBIO, ICEBIO) showed that TNFI adherence was lower in obese patients, especially among men. Obese patients had a median TNFI survival of 2.5 years vs. 5.9 years in non-obese patients (P < 0.01). Moreover, obese patients were less likely to achieve a EULAR good or moderate response (55% vs. 65% non-obese; P = 0.02). Thus obesity was associated with higher disease activity and seemed to diminish response and adherence to TNFIs in PsA.  (http://bit.ly/2Bi1Rw6)

Comorbidity and Drug Outcomes.  Patients with comorbidities have poorer quality of life measures, take more medications and see more physicians.  Additionally, comorbidity negatively influences therapeutic responses and clinical outcomes. 

A study of 635 patients with RA, SpA and PsA showed that after assessing comorbidity with a comorbidity index, this score was inversely correlated with the persistence of biologic treatments and clinical outcomes. (http://bit.ly/2MXpHOQ)

A recent study from the Australian Rheumatology Database compared RA and PsA patients and found that psoriatic arthritis patients had a nearly a 2 fold greater frequency of comorbidities (depression, HTN, DM, hyperlipidemia, ischemic heart disease) than RA patients.  (http://bit.ly/2MMr5nC)

These are but a few examples of a growing and serious impediment to optimal medical care. The question is what can be done about comorbidity and clinical outcomes?  Consider the following for adoption:

  • Every patient must have a primary care physician and must be seen annually and comprehensively by their PCP.
  • Every patient must have effective and ongoing communication between their PCP and specialists caring for the same patient.
  • All patients must have vital signs including weight and BMI calculations at every visit; 
  • Specialists (e.g., rheumatologists) must proactively seek, identify and provide initial management of common comorbidities – obesity, HTN, diabetes, hyperlipidemia, etc....then refer to PCP;
  • Every physician must counsel “at risk” patients with regard to the hazards and control of obesity, smoking, hypertension and hyperlipidemia.

 

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

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