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Comment on: ‘Successful remission with tofacitinib in a patient with refractory Takayasu arteritis complicated by ulcerative colitis’ by Kuwabara et al
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  1. Valeria Rios Rodriguez1,
  2. Judith Rademacher1,2,
  3. Mikhail Protopopov1,
  4. Murat Torgutalp1,
  5. Hildrun Haibel1,
  6. Janis Lucas Vahldiek3,
  7. Ann-Christin von Brünneck4,
  8. Safwan Omran5,
  9. Denis Poddubnyy6,
  10. Fabian Proft1
  1. 1Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Germany
  2. 2Berlin Institute of Health, Berlin, Germany
  3. 3Department of Radiology, Charité Universitätsmedizin, Berlin, Germany
  4. 4Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany
  5. 5Clinic of Vascular Surgery, Charité Universitätsmedizin, Berlin, Germany
  6. 6Epidemiology Unit, German Rheumatism Research Center, Berlin, Germany
  1. Correspondence to Dr Fabian Proft, Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, 12203 Berlin, Germany; Fabian.Proft{at}charite.de

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We read with great interest the case report by Kuwabara et al.1 With this comment, we want to share the case of a 38-year-old male patient with a long history of radiographic axial spondyloarthritis (r-axSpA)—with HLA-B27 positivity, peripheral joint involvement and skin psoriasis—complicated by Takayasu arteritis (TAK), showing a favourable response to a combination therapy of Tofacitinib (TOF) and methotrexate (MTX) with the readers of the ‘Annals of the Rheumatic Diseases’.

The r-axSpA was well-controlled under tumour necrosis factor alpha inhibiton with infliximab and MTX between 2013 and 2017 (figure 1). At the beginning of 2017, he presented a worsening of his disease with peripheral arthritis/enthesitis in addition to fatigue and myalgia of the neck and shoulder region. Therefore, in 2017/2018, the treatment was changed to golimumab, and then—due to persistent symptoms—to etanercept, secukinumab and certolizumab pegol and additionally MTX was switched to sulfasalazine (SSZ). All treatment courses failed to achieve an adequate disease control (figure 1). Additionally, the patient self-administered oral prednisolone (PSL) (between 50 and 15 mg daily) during that period.

Figure 1

Treatment and CRP courses overview of the different treatment strategies and the CRP course over time. bDMARDs, biological disease modifying antirheumatic drugs; CRP, C reactive protein; csDMADRs, conventional synthetic disease modifying antirheumatic drugs; tsDMARDs, targeted synthetic disease modifying antirheumatic drugs.

In December 2018, certolizumab pegol and SSZ were discontinued because of persistent symptoms described above, in addition to progressive weight loss as well as C reactive protein (CRP) elevation (51.3 mg/L) and treatment with TOF (5 mg two times per day) was initiated (figure 1). A week later, the patient presented with tongue swelling, muffled speech and headache. The clinical examination revealed a hypoglossal paresis. An urgent CT angiography (CT-A) showed an aneurysm of 1.7 cm of the left external carotid artery (figure 2A) and a thickening of the wall of the carotid arteries. The aneurysm was resected and TOF therapy was stopped as a precaution measure due to a temporal relationship with the acute vascular event. On the next day, the patient experienced symptoms of dysesthesia and pain in the ulnar nerve region. Ultrasound revealed an extension of the right subclavian artery, which CT-A proved to be a new pseudoaneurysm of 2.7 cm (figure 2B). This aneurysm was also resected, and a vascular prosthesis was incorporated (figure 2C).

Figure 2

CTangiography, intraoperative and histological images. (A) 3D-Volume Rendering Technique (VRT) and coronal reconstructions of the neck. 1.7 cm diameter pseudoaneurysm of the left external carotid artery (red arrows). (B) 3D-VRT and coronal reconstructions of the upper thoracic aperture. 2.7 cm diameter pseudoaneurysm of the right subclavian artery (red arrows). (C) Aneurysmatectomy, replacement of the artery with subclavio-subclavian bypass using 6 mm polytetrafluorethylen (PTFE) graft. (D) Higher magnification of arterial wall reveals lymphozytes, plasma cells, macrophages and several giant cells (marked with black arrows) partially rimming necrosis.

The histopathological analysis of the aneurysm of the external carotid artery showed a lympho-histiocytic vessel wall infiltration with the presence of giant cells (figure 2D) compatible with TAK. Therefore, we started treatment with systemic corticosteroids (methylprednisolone 500 mg intravenously) and tocilizumab 8 mg/kg body weight intravenously every 4 weeks together with a tapering scheme of oral PSL starting from 80 mg daily (figure 1). However, the patient experienced a flare of his SpA-symptoms. Therefore, we switched the treatment back to TOF 5 mg two times per day together with MTX 15 mg weekly. This combination led to a rapid improvement of SpA symptoms with no new vascular episodes. The follow-up CT-A 6 months after reinitiation of the JAK-inhibition showed no further symptom progression and the CRP remained normal; PSL was tapered and subsequently stopped, while the combination therapy of TOF and MTX was continued and the patient is now in sustained clinical and laboratory remission for 12 months (figure 1).

Several cohort studies have recently reported that SpA features are common in TAK patients, and suggested potential shared genetic or immunopathogenic mechanisms.2 3 For that reason, we believe it is utterly important to find therapeutic regimens showing efficacy for both diseases. Our case underlines the potential efficacy of JAK inhibition (in combination with MTX) in the treatment of TAK4; this idea is supported by the data published by Regnier et al in this journal presenting in vitro data as well as a case series of three TAK patients receiving baricitinib and ruxolitinib treatment,5 and corroborates the promising data on TOF treatment in aknylosing spondylitis6 illustrating potential future treatment options for both diseases.

Acknowledgments

We thank the patient giving his consent to this publication.

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Footnotes

  • Contributors VRR, DP and FP wrote the manuscript. JR, VRR, FP, HH and DP were involved in the clinical care of the patient. JLV provided the radiology figures and A-CvB the histopathological images. SO collected the clinical data of vascular surgery. MP, MT and DP contributed to the discussion and edited the manuscript. All authors read and approved the manuscript in its final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests VRR: speaker and consulting fees from AbbVie and Novartis. JR: has nothing to disclose. MP: speaker and consulting fees from AbbVie and Novartis. MT: has nothing to disclose. HH: speaker and consulting fees from Janssen, MSD, Novartis, Pfizer and Roche. JLV: has nothing to disclose. A-CvB: has nothing to disclose. SO: has nothing to disclose. DP: research grants from AbbVie, Eli Lilly and Company, MSD, Novartis, and Pfizer; speaker and consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, MSD, Novartis, Pfizer, Roche and UCB PharmaFP: research grants from Novartis; speaker and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche and UCB Pharma.

  • Patient and public involvement The patient provided written consent with publication of his personal data in this case report.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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