The practical use of baricitinib and ixekizumab reflected in real world data and case studies

Wednesday, 19 May 2021


A recent webcast with an international panel of experts and featuring real world data and case studies provided insights into the practical use of baricitinib for rheumatoid arthritis and ixekizumab for psoriatic arthritis.

The webcast was sponsored by Eli Lilly, and the discussion was moderated by Professor Bruce Kirkman, Professor of Translational Rheumatology at King’s College London, and Consultant Rheumatologist at Guy’s & St Thomas’ NHS Foundation Trust, UK. The panel of experts included Australian rheumatologist Professor Andrew Ostor from Cabrini Medical Centre, Melbourne, Victoria.  

Registry and hospital data reveals patterns of use and effectiveness of baricitinib

Southampton rheumatologist and epidemiology researcher Professor Chris Edwards presented baricitinib real world data drawn from a large registry and from local hospital sources, followed by a case study illustrating the potential benefits of baricitinib monotherapy in a patient reluctant to continue methotrexate (MTX) or to use injectable therapies.

The data from the British Society of Rheumatology Biologics Registry included 390 patients treated with baricitinib. The average age of baricitinib-treated patients was 60 years, and patients had a mean Disease Activity Score (DAS) 28-ESR score of 5.6 and significant functional disability (mean Health Assessment Score Disability Index [HAQ-DI]: 1.7). Mean disease duration was 12.9 years. The majority of patients (84%) were taking the 4mg dose, and baricitinib monotherapy was used in 38% of patients.

Follow-up data in 129 patients showed that 76% were continuing to use baricitinib. Those who discontinued did so because of lack of efficacy (21%) or adverse events (71%). For those who continued, around 45% were in remission or with low disease activity. At follow-up, there was also a fall in patients categorised in the moderate-to-severe disease categories.

Local data from three hospitals in the UK  showed a similar rate of patients using baricitinib monotherapy (37%). The majority (70%) had used a biologic therapy previously. Professor Edwards noted, “People tend to use [JAK inhibitors] initially in those patients who have the most severe disease with longest disease duration and also those who have experienced failures on other biologic therapies.”

Baricitinib in patients intolerant to csDMARDs

Professor Edwards presented a case study of a 72-year-old female patient with seropositive rheumatoid arthritis diagnosed 10 years previously and commenced on oral MTX with the addition of sulfasalazine (1g twice daily), which was subsequently discontinued due to gastrointestinal intolerance

MTX was changed to subcutaneous administration, but after a flare of disease that necessitated a number of intramuscular methylprednisolone injections, the patient chose to return to the oral formulation. Her disease became increasingly difficult to control (DAS28: 6.62) despite commencement of hydroxychloroquine.

To bring her disease under control, etanercept was considered but the patient wanted to avoid injectable therapy and thus commenced baricitinib. She spontaneously discontinued MTX when she began to improve on baricitinib, eventually achieving a DAS28 score within the range of remission (1.33).

First-line use of baricitinib in patients failing csDMARDs

Professor Ostor from Melbourne has had extensive experience with baricitinib, with his group practice having treated around 450 patients with this therapy. He presented data showing that only around one third of patients prescribed baricitinib had previously been treated with biologic therapies. This is in contrast to the data from the United Kingdom where most patients had previously failed a biologic before being treated with a JAK inhibitor. The data showed that around 60% of patients taking baricitinib also take a conventional synthetic disease modifying anti-rheumatic drug (csDMARD), predominantly MTX.

Professor Ostor presented the case of a 61-year-old female with a severe anti-CCP rheumatoid factor-positive rheumatoid arthritis who had not responded well to csDMARDS.

The patient had presented after two months of increasing pain and stiffness in the hands and feet, early morning stiffness, and loss of strength and dexterity. Fatigue was also a major issue, and together with the other symptoms was significantly impacting on her function and quality of life. Along with a statin and antihypertensive, she was taking regular paracetamol and naproxen, which were not alleviating her arthritis symptoms. X-rays of her hands showed no rheumatoid arthritis changes.

After a six-week course of prednisolone and six months of csDMARD therapy, her arthritis flared up. Her DAS score was 5.6 and she experienced ongoing pain, stiffness and swelling, with profound fatigue that caused her to consider giving up work.

The patient commenced baricitinib (4mg daily) and noticed an improvement after two weeks. Apart from some mild residual fatigue and numbness in the left hand, she was back to normal after two months. Her DAS score had reduced (2.5) and her arthritis was not interfering with her function or her quality of life.

At around 12 months of therapy, she experienced an episode of shingles, which improved with antivirals and settled quickly. The patient stopped baricitinib for two weeks but was keen to restart due to the benefits she had experienced in relation to symptoms, function and fatigue. She subsequently discontinued MTX, with no deterioration in her condition, and continues on baricitinib monotherapy.

Professor Ostor reported, “She is back to enjoying life and really feels that the medication has given back her quality of life, and given back her life in the way she wants to lead it.”

Psoriatic arthritis (PsA) case study highlights the rapid action of ixekizumab

Associate Professor Valderilio Feijo Azevedo from Brazil presented a case study of ixekizumab in a 42-year-old patient with psoriatic arthritis who was diagnosed in 2010 and had been treated with MTX (25mg weekly) from 2012 until 2019, before presenting with worsening symptoms.

Ixekizumab was added to therapy and after eight weeks there was a marked decrease in DAS28, from 4.5 to 2.7, and PASI score from 28 to 4.  Her hand synovitis was improved, although she continued to have low synovitis in her third right distal interphalangeal joint (DIP). At this stage, the methotrexate was reduced to 10mg weekly.

After six months, the patient achieved minimal disease activity (MDA) 6/7, with significant improvements in her skin. After one year of treatment, MTX was withdrawn due to continued good clinical response in skin and joints, although there was continued ankyloses in her third right DIP. “We had a satisfactory response in all domains of psoriatic arthritis – all manifestations – in treating this case of psoriatic arthritis,” said A/Prof Azevedo.

A/Prof Azevedo pointed out that the continued good clinical response with ixekizumab upon withdrawal of MTX in this patient is in line with data from a pre-specified subgroup analysis of the SPIRIT H2H trial1, which showed consistent response rates with ixekizumab monotherapy and with the combination of ixekizumab plus methotrexate. In contrast, concomitant csDMARD with adalimumab resulted in higher response rates than with adalimumab monotherapy.1

Ixekizumab impact on PsA domains beyond arthritis

Professor Johannes Grisar from Vienna explained that 20-30% of psoriasis patients develop psoriatic arthritis (PsA) during the course of their disease.2 He noted that although the most common symptom is arthritis, a large proportion of patients also suffer enthesitis, dactylitis, nail psoriasis and axial involvement.

“When it comes to pathophysiology, we know that IL-17 is a pivotal cytokine which perpetuates the disease process,” Professor Grisar explained. “The blockade of this cytokine with ixekizumab is a proven mode of action to halt the disease,”3 he said.

Professor Grisar presented a case of a 44-year-old married woman who had been referred to the clinic by a dermatologist, who the patient had consulted for management of her psoriasis for cosmetic reasons.

“Important to note, she had psoriatic arthritis, but she did not only suffer from arthritis itself, but several domains also were affected such as enthesitis, dactylitis and nail psoriasis,” said Professor Grisar.

The patient commenced MTX, which was poorly tolerated and discontinued after four weeks. She then commenced ixekizumab, and after 10 weeks of therapy the enthesitis and dactylitis were in full remission. She still had very mild swelling of the left distal interphalangeal joint of the fifth finger but no swelling in the fourth finger. The nail psoriasis improved, and she no longer suffered from back pain. At four months, the patient had full remission in all domains, and no adverse events.

Professor Grisar concluded by presenting a short summary of the most frequent adverse events with ixekizumab in the clinical trials,4 which include upper respiratory tract infections, similar to other immunosuppressive therapies, tinea and herpes simplex infections. “Blood and lymphatic system disorders are, in contrast, uncommon, as are immune system disorders,” he said.

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) and Taltz® (link) full product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.

References

  1. Smolen et al. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52. Ann Rheum Dis 2020;79:1310-1319. https://ard.bmj.com/content/annrheumdis/79/10/1310.full.pdf
  2. Ritchlin CT et al Psoriatic Arthritis. N Engl J Med 2017;376(10):957-970 https://pubmed.ncbi.nlm.nih.gov/28273019/
  3. Mease PJ et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naïve patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76:79–87 https://pubmed.ncbi.nlm.nih.gov/27553214/
  4. Combe B et al Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis. Arthritis Res Ther 2020;22:14 https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-020-2099-0

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