Rheumatoid Arthritis

Unmet Needs in RA

Overview

Although there have been many advances in treatment, many patients with RA are not optimally treated and struggle with symptoms which impact their daily lives.1

Furthermore, achieving remission and maintaining it over time remain challenging.2,3

Even for patients with moderate to high disease activity, there are obstacles to the T2T approach of switching DMARDs, including irreversible joint damage, patient concerns of potential side effects, and comorbidities.4

Treatment and responses

Only 11% of patients with recent-onset RA treated with csDMARDs achieved sustained remission at all follow-ups (Year 3, Year 4, and Year 5)2

As few as 32% of patients with RA achieve remission after 12 months of treatment, and only 64% after 24 months3

54% of patients not in remission at 6 months did not switch therapy5

  • ~1/3 of patients do not achieve a long-term response6
  • Up to 50% of patients discontinue treatment due to loss of efficacy, AEs, and patient preference (e.g., frequency of administration)7-9
  • ~50% of patients initiating their first biologic discontinue it within 3 to 5 years8,9
  • Switching to a drug with a different MOA vs cycling of TNFα inhibitors was associated with better treatment persistence and clinical outcomes10
  • After failure of a bDMARD, persistence with the next line of therapy differs by drug class11
  • Persistency among monotherapies at 6 months*:

- non-TNFi or JAKi = 79%
- csDMARD = 70%
- TNFi = 68%

  • Loss of treatment persistence can have multiple impacts12,13:

- Reduced clinical effectiveness
- Increased morbidity and mortality
- Increased healthcare utilisation (including longer hospital stays)

  • Response to targeted therapies diminishes with every subsequent line of treatment8

Safety

  • ­↑ incidence of systemic complications in patients with RA,14 -16 potentially due to the immune dysfunction and inflammatory disease activity associated with RA 
  • Complications include16:

- Atherogenesis, MI, heart failure
- CVA
- Low stress tolerance
- Low bone mineral density
- Insulin resistance
- Malignancies (lymphoma, lung cancer)

  • 50% more likely to develop an infection17
                 
                   - ~2X increased risk of HZ in patients with RA compared to the general population18
                 
  • ↑ risk of CHD in patients with RA correlates with number of inflamed joints15
  • 2.4X higher risk of developing a VTE19

Comorbidities

  • ↑ number of comorbidities correlates with functional disability, reduced likelihood of achieving remission, and decreased QoL20-22
  • >90% of patients with RA have at least one comorbidity, and 60% have 3 or more22

        - Comorbidities impacting patients with RA include CVD, infections, respiratory disease, osteoporosis, diabetes, and
          depression23,24

  • 50% increased risk of CVD morality25
  • 60% to 80% of patients have pulmonary manifestations26
  • 50% increased risk for diabetes27

Identifying Comorbid Conditions in Patients with RA

Download the comorbidity infographic.

Patient impact

  • Over >20 years, PROs have deteriorated28
    - Patients have fewer swollen joints, less inflammation, and lower CRP levels but report more fatigue, more pain, and higher disease activity
  • Patients with RA are predominantly affected by pain, fatigue, depression, and reduce HRQoL1,29;
    - Higher Pain VAS scores correlate with lower physical and mental QoL, including reduced physical and social functioning30
    - Fatigue affects up to 80% of patients, 63% of whom are in remission31,32
    - Diagnosis of clinical depression was missed in 48% of patients with RA33

  • Lower SF-36 scores in all domains, including global health and vitality34
  • ~2/3 of patients experience activity and work impairment35
  • Impact of RA cannot be fully assessed until PROs are incorporated into disease measurements29

Related

Clinical Outcomes

Check out a summary of key clinical outcome measures

About JAK-STAT

Explore and learn more about the pathogenesis of RA

AE, adverse event; bDMARD, biologic disease-modifying antirheumatic drug; CHD, coronary heart disease; CRP, C-reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; CVA, cerebrovascular accident; CVD, cardiovascular disease; DAS, Disease Activity Score; DMARD, disease-modifying antirheumatic drug; HAQ, Health Assessment Questionnaire; HRQoL, health-related quality of life; HZ, herpes zoster; JAKi, Janus kinase inhibitor; MI, myocardial infarction; MOA, mechanism of action; PRO, patient-reported outcome; QoL, quality of life; RA, rheumatoid arthritis; SF-36, 36-item Short-Form Health Survey; T2T, treat to target; TJC28, Tender Joint Count Over 28 Joints; TNFi, tumour necrosis factor inhibitor; TNFα, tumour necrosis factor alpha; VAS, visual analogue scale; VTE, venous thromboembolism.

* Similar results among combination therapies.


REFERENCES

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