Medicines

Going beyond: long-term treatment results with baricitinib in rheumatoid arthritis


At the 2021 European Congress of Rheumatology (EULAR), Eli Lilly & Company sponsored a symposium discussing long-term treatment results with baricitinib in rheumatoid arthritis (RA). It included a presentation from Professor Peter Taylor, the Norman Collisson Professor of Musculoskeletal Sciences at Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, and Fellow of St. Peter’s College Oxford (United Kingdom). Here we provide a snapshot of his presentation, covering current challenges in achieving disease control as well as data supporting the use of baricitinib in combination with methotrexate (MTX).

Challenges in achieving disease control in RA

Professor Taylor opened his discussion by outlining the current challenges clinicians face in achieving low disease activity (LDA) or remission.1–4 These include failure to respond to the initial DMARD course, intolerance of MTX monotherapy and loss of treatment response over time.1–4 In addition, the subjective aspects of disease may be barriers to disease control. Aspects such as pain, treatment safety, comorbidities, quality of life limitations and discordance between the patient and their physician. 4–6 Professor Taylor pointed out that “even with the correct treatment strategy, at least 25% of patients with RA do not achieve remission or LDA”.4 However, if clinicians are able to achieve LDA earlier rather than later, chances are the long-term outcomes will be better.7

Early control can be sustained through 12 months and beyond – up to 3 years with baricitinib + MTX

Professor Taylor then showcased highlights from the RA-BEAM and RA-BEYOND clinical trials. The RA-BEAM study was a randomised, double-blind, placebo and active controlled (adalimumab) study of 1,305 adult patients who, despite being stable on treatment, had an inadequate response to MTX. Exclusion criteria included prior DMARD use. Patients were randomised to receive either baricitinib 4 mg QD + MTX (n=487), placebo + MTX (n=488) then allowed to switch to baricitinib 4 mg QD + MTX (if no response; n=434) or adalimumab 40 mg Q2W + MTX (n=330). The placebo group were allowed to switch to baricitinib at 24 weeks, and the study continued to 52 weeks.8 The RA-BEYOND was an open-label extension of the RA-BEAM trial, where patients could remain on or switch to baricitinib 4 mg QD, still with background MTX, including patients previously in the adalimumab arm of RA-BEAM.9

Results of the RA-BEAM study showed that the proportion of patients achieving LDA with baricitinib + MTX was significantly higher than with adalimumab + MTX at weeks 12 and 52 (Table 1).8 These results were sustained over 3 years, with an SDAI ≤11 seen in 59% of patients treated with baricitinib at Week 148 and 61% of patients initially treated with adalimumab in RA-BEAM (before switching to baricitinib in RA-BEYOND) in the more conservative NRI analysis set.10 Remission, defined as SDAI ≤3.3, was also sustained over 3 years, with 24% of patients initially treated with baricitinib in remission, 28% of patients initially treated with adalimumab and 23% of patients initially treated with placebo at Week 148, also in the conservative NRI analysis set.10 Interestingly, remission response rates increased in patients following the switch from placebo to baricitinib from week 24 to week 52, and were then maintained through week 148.10

Table 1. Proportion of patients achieving SDAI ≤11 and CDAI ≤10 at weeks 12 and 52 in the RA-BEAM study8,10

SDAI ≤11 CDAI ≤10
Week 12 Week 52 Week 148 Week 12 Week 52 Week 148
Baricitinib 42% 57% 59% 40% 57%
Adalimumab 35% 49% 61% 33% 49%
P value vs adalimumab p≤0.05 p≤0.05 NS p≤0.05 p≤0.05

NS=p value not stated.

Radiographic progression at 5 years

In the RA-BEAM study the majority of patients on baricitinib showed no progression over 5 years.11 When Professor Taylor took a closer look at the radiographic progression data, he noted that progression of structural joint damage at 5 years was significantly inhibited with baricitinib (Figure 1).11,12

Figure 1. Change from baseline in A) modified total Sharp score (mTSS), B) erosion score (ES) and C) joint space narrowing (JSN).11,12

Bari=baricitinib; ADA=adalimumab; PBO=placebo.

What about safety in the long term?

In the RA-BEAM and RA-BEYOND trials over 3 years, only 3.6% of MTX-IR patients treated with baricitinib 4 mg discontinued due to lack of efficacy. This low discontinuation rate indicated that baricitinib 4 mg remained efficacious over the long term.10 Beyond these two studies, safety has been assessed across multiple clinical trials in more than 3,770 patients treated for up to 8.4 years.13

One important aspect these safety trials looked at was thrombosis. Patients with RA have an increased risk of developing venous thrombotic events (VTE) such as deep vein thrombosis (DVT) or pulmonary embolism (PE).14 In fact, the incidence rate for VTE among RA patients was shown to be two to three times higher than the rate for people without RA.14 It is thought that this is due to overlaps in the pathophysiology of both RA and thrombosis, for example systemic inflammatory response and subsequent microparticle release which is associated with thrombosis.15–17 When looking at the data, the incidence rate of DVT/PE has remained stable over time with cumulative exposure to baricitinib (Figure 2).18,19

Figure 2. Incidence rates of DVT/PE remained stable over time with cumulative exposure to baricitinib up to 8.4 years18,19

a Data up to February 13, 2018; b Data up to September 1, 2019.

Professor Taylor concluded his presentation noting that baricitinib has demonstrated a consistent efficacy and safety profile across a large population of patients.13,20 In 2021, there is now a large body of evidence examining the use of baricitinib across a large population of patients. As a once-daily oral treatment, it has the potential to achieve disease control early and maintain it in the longer term.8,13,20,21

 

[Footnote]

CDAI=Clinical Disease Activity Index; CI=confidence interval; DMARD=disease-modifying antirheumatic drug; IR=inadequate responder; LS=least squares; NRI=non-responder imputation; PBO=placebo; PYE=patient years of exposure;  QD=once a day; Q2W=every two weeks; SDAI=Simplified Disease Activity Index; SE=standard error.

 

This article was commissioned by Eli Lilly Australia Pty Ltd. The content is independent and based on studies and the author’s opinion. The views expressed do not necessarily reflect the views of Eli Lilly. Before prescribing please review the Olumiant® (link) full product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.

References

  1. Taylor PC, et al. Rheumatol Int 2016;36(5):685-695.
  2. Aletaha D, Smolen JS, JAMA 2018;320(13):1360-1372.
  3. Bello AE, et al. Open Access Rheumatol 2017;9:67-69.
  4. Rubbert-Roth A, et al. Arthritis Res Ther 2009;11(Suppl 1):S1.
  5. Tymms K, et al. Arthritis Care Res 2004;66(2):190-196.
  6. Cordtz RL, et al. Ann Rheum Dis 2018;77(2):281-288.
  7. Combe B, et al. Ann Rheum Dis 2015;74(4):724-729.
  8. Taylor PC, et al. N Engl J Med 2017;376:652-662 (plus supplementary appendix and protocol).
  9. gov. https://clinicaltrials.gov/ct2/show/NCT01885078
  10. Smolen JS, et al. Rheumatology 2021; 60(5):2256-2266.
  11. van der Heijde D, et al. Poster presented at ACR annual meeting 2020. Abstract 1235.
  12. van der Heijde D, et al. RMD Open 2019;5(1):e000898.
  13. Genovese MC, et al. Poster presented at EULAR annual meeting 2020. FRI0123.
  14. Kim SE, et al. Arthritis Care Res 2013;35(10):1600-1607.
  15. Levi M, et al. Circulation 2004;109(22):2698-704.
  16. Zoller B, et al. Am J Cardiovasc Dis 2012;2(3):171-83.
  17. Hoppe B, et al. Nat Rev Rheumatol 2012;8(12):738-46.
  18. Genovese MC, et al. Ann Rheum Dis 2019;78(Suppl 2):308-309.
  19. Genovese M, et al. Poster presented at EULAR annual meeting 2020. Abstract 847.
  20. Keystone EC, et al. Ann Rheum Dis 2017;76(11):1853-1861.
  21. Olumiant (baricitinib) Approved Product Information. April 2021

Already a member?

Login to keep reading.

OR
Email me a login link
logo

© 2022 the limbic