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Background: Autoinflammatory syndromes are characterized by dysregulation of innate immunity and recurrent episodes of fever, cutaneous and other. Janus Kinase inhibitors (JAKINIB) may inhibit innate and acquired immunity. They have been approved in several immune mediated diseases, but not in autoinflammatory syndromes.
Objectives: To assess the efficacy and safety of JAKINIB in refractory autoinflammatory syndromes.
Methods: Study of patients from a single University Hospital and Literature review of refractory autoinflammatory syndromes treated with JAKINIB.
Results: We have identified 2 cases in our hospital. One of them was a 25-year-old girl diagnosed with Blau syndrome refractory to different conventional and biological therapies. Tofacitinib (TOFA) had a good clinical response but was switched to Bariticitinib (BARI) due to severe lymphopenia. The 2nd patient was a 65-year-old man, diagnosed with an autoinflammatory syndrome (WDR1 mutation) and policytemia vera (positive JAK-2; V617F mutation). Based on the JAK2 mutation, BARI was started with complete improvement. In literature review, we found 59 patients (41 women/ 18 men), mean age 38.1±13 years. TOFA (n=23) was the most used JAKINIB, followed by BARI (n=20) and Ruxolitinib (RUXO) (n=16). After starting JAKINIB treatment, most patients presented clinical complete (n=45, 76.3%) or partial (n=11; 18.6%) improvement, only 3 (5.1%) did not respond. (
Case reports and literature review of patients with refractory autoinflammatory syndromes treated with Janus Kinase Inhibitors.
| Study, year | Cases, n | Age/Sex | Underlying Disease | JAKINIB | Previous immunosuppressive treatment | Clinical Evolution |
|---|---|---|---|---|---|---|
| (Ref ) | ||||||
| García-Robledo et al, 2022 (1) | 1 | 16, F | FMF | TOFA | MTX, TCZ, CANA | C.I. |
| Gök K et al, 2017 (2) | 1 | 27, F | FMF | TOFA | MTX | C.I. |
| Forbes et al, 2018 (3) | 17 | 12.4±7.5*, F=9 | STAT1 and TAT3 GOF | RUXO (n=16)TOFA (n=1) | AZA(n=1), iv immunoglobulins (n=3), CsA (n=2), RTX (n=2) ECU (n=1), ANA (n=1), MTX (n=2), CYC (n=2), MMF (n=1) | C.I. (n=14)N.R. (n=3) |
| Landhari et al, 2020 (4) | 1 | 43, F | AOSD | BARI | MTX, SSZ, ANA, IFX, TCZ, ABA | C.I. |
| Sánchez et al, 2018 (5) | 18 | 12.5 (1.2-24.1) ** (F=12) | CANDLE n=10 | BARI | Immunomodulators (n=17) | C.I. (n=16) |
| CANDLE-related n=4 | ||||||
| SAVI n=4 | Biologics (n=13) | P.I. (n=2) | ||||
| Karadeniz et al, 2020 (6) | 4 | 1. 28, M | FMF | TOFA | 1. AZA, MTX, ANA, CANA, IFX, TCZ | 1. C.I. |
| 2. 58, F | 2. SSZ, MTX, LEF, ANA, ADA, TCZ | 2. C.I. | ||||
| 3. 64, F | 3. SSZ, MTX, LEF, HCQ, CsA, ADA, ABA, ANA | 3. P.I. | ||||
| 4. 43, F | 4. SSZ, ADA, ETA, ANA | 4. C.I. | ||||
| Hu et al, 2020 (7) | 14 | 34,8±14* | AOSD | TOFA | MTX (n= 8), HCQ (n=5), CsA (n=5), TCZ (n=2), ANA (n=1) | C.I. (n=7) |
| F=12 | P.I. (n=7) | |||||
| Honda et al, 2020 (8) | 1 | 68, F | AOSD | TOFA | TCZ, Tacrolimus, CYC | P.I. |
| Present study, 2022 | 2 | 1.25, F | 1. Blau Syndrome | 1.TOFA/BARI | 1. MTX, ETN, ANA, ABA | 1. C.I. |
| 2. 64, M | 2. Autoinflammatory syndrome (WDR1 mutation) | 2.BARI | 2. ANA | 2. C.I. |
*Mean±Standard deviation, **Median (range)
Abbreviations: ABA: abatacept, ADA: adalimumab, ANA: anakinra, AOSD: adult onset Still disease, AZA: azathioprine, BARI: baricitinib, CANA: canakinumab, CANDLE: Cronichle atypical neutrophilic dermatosis with lypodistrophy and elevated temperature, C.I.: Complete improvement, CsA: cyclosporine A, ECU: eculizumamb, ETN: etanercept, FMF: familial mediterranean fever, HCQ: hydroxychloroquine, IFX: infliximab, LEF: leflunomide, MMF: mycophenolate mofetil, MTX: methotrexate, N.R: no response, P.I.: partial improvement, RUXO: ruxolitinib, SAVI: STING-associated vasculopathy with onset in infancy, SSZ: sulfasalazine, STAT1 and STAT3 GOF: STAT1 and STAT 3 gain of function, TCZ: tocilizumab, TOFA: tofacitinib.
Conclusion: JAKINIB may be an effective therapy in autoinflammatory syndromes refractory to conventional and/or biologic therapy.
REFERENCES:
[1]García-Robledo. Rheumatology. 2019; 58:553-554.
[2]Gök. Acta Reumatol Port. 2017; 42:88-90.
[3]Forbes. J Allergy Clin Immunol. 2018; 142:1665-1669.
[4]Landhari. Rheumatology. 2019; 58:736–737.
[5]Sánchez. J Clin Invest. 2018; 128:3041-3052.
[6]Karadeniz. Rheumatology. 2020; 40: 169-173.
[7]Hu. Ann Rheum Dis. 2020; 79: 842-844.
[8]Honda. Scand J Rheumatol. 2020; 49:336-338
Disclosure of Interests: Carmen Álvarez-Reguera: None declared, Diana Prieto-Peña: None declared, Lara Sanchez-Bilbao: None declared, Alba Herrero-Morant: None declared, David Martínez-López: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Janssen and Roche., Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche.