Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis
Abstract Introduction The safety of tofacitinib in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in clinical studies of ≤ 4 and 9.5 years, respectively. Post-marketing surveillance (PMS) data for tofacitinib from spontaneous and voluntary adverse event (AE) reports ha...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-07-01
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| Series: | Rheumatology and Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s40744-023-00576-8 |
| _version_ | 1797414021591203840 |
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| author | Gerd R. Burmester Laura C. Coates Stanley B. Cohen Yoshiya Tanaka Ivana Vranic Edward Nagy Irina Lazariciu All-shine Chen Kenneth Kwok Lara Fallon Cassandra Kinch |
| author_facet | Gerd R. Burmester Laura C. Coates Stanley B. Cohen Yoshiya Tanaka Ivana Vranic Edward Nagy Irina Lazariciu All-shine Chen Kenneth Kwok Lara Fallon Cassandra Kinch |
| author_sort | Gerd R. Burmester |
| collection | DOAJ |
| description | Abstract Introduction The safety of tofacitinib in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in clinical studies of ≤ 4 and 9.5 years, respectively. Post-marketing surveillance (PMS) data for tofacitinib from spontaneous and voluntary adverse event (AE) reports have been published for RA, but not PsA. To inform the real-world safety profile of tofacitinib in PsA, we evaluated AE reports submitted to the Pfizer safety database (including RA data for context). Methods Endpoints included AEs, serious AEs (SAEs), AEs of special interest (AESIs; serious infections, herpes zoster, cardiovascular events, malignancies, venous thromboembolism), and fatal cases. Exposure was estimated using IQVIA global commercial sales data. Number, frequency, and reporting rates (RRs; number of events/100 patient-years’ [PY] exposure) were summarized by indication and formulation (immediate release [IR] 5 or 10 mg twice daily], modified release [MR] 11 mg once daily, or all tofacitinib). The data-collection period differed by indication (PsA: 14 December 2017 [US approval, IR/MR] to 6 November 2021; RA: 6 November 2012 [US approval, IR] to 6 November 2021; MR approval, 24 February 2016). Results A total of 73,525 case reports were reviewed (PsA = 5394/RA = 68,131), with 20,706/439,370 PY (PsA/RA) of exposure. More AEs were reported for IR versus MR (IR/MR: PsA = 8349/7602; RA = 137,476/82,153). RRs for AEs (IR/MR: PsA = 59.6/113.4; RA = 44.0/64.8) and SAEs (PsA = 8.1/13.6; RA = 8.0/9.5) were higher with MR versus IR. AE RRs (RA) in the first 4 years after IR approval were 95.9 (IR; 49,439 PY) and 147.0 (MR; 2000 PY). Frequency of SAEs, AESIs, and fatal cases was mostly similar across formulations and indications. The most frequently-reported AE Preferred Terms (PsA/RA) included drug ineffective (20.0%/17.8%), pain (9.7%/10.6%), condition aggravated (9.9%/10.5%), headache (8.8%/7.9%) and, for PsA, off-label use (10.5%/3.4%). Conclusions Tofacitinib PMS safety data from submitted AE reports were consistent between PsA and RA, and aligned with its known safety profile. Exposure data (lower MR versus IR; estimation from commercial sales data), reporting bias, reporter identity, and regional differences in formulation use limit interpretation. |
| first_indexed | 2024-03-09T05:27:03Z |
| format | Article |
| id | doaj.art-34b105e8c7c24f45a0dae2316f33af1c |
| institution | Directory Open Access Journal |
| issn | 2198-6576 2198-6584 |
| language | English |
| last_indexed | 2024-03-09T05:27:03Z |
| publishDate | 2023-07-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Rheumatology and Therapy |
| spelling | doaj.art-34b105e8c7c24f45a0dae2316f33af1c2023-12-03T12:35:55ZengAdis, Springer HealthcareRheumatology and Therapy2198-65762198-65842023-07-011051255127610.1007/s40744-023-00576-8Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid ArthritisGerd R. Burmester0Laura C. Coates1Stanley B. Cohen2Yoshiya Tanaka3Ivana Vranic4Edward Nagy5Irina Lazariciu6All-shine Chen7Kenneth Kwok8Lara Fallon9Cassandra Kinch10Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin BerlinNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research CentreMetroplex Clinical Research Center and Department of Internal Medicine, The University of Texas Southwestern Medical CenterFirst Department of Internal Medicine, University of Occupational and Environmental Health JapanPfizer LtdPfizer LtdPfizer IncPfizer IncPfizer IncInflammation and Immunology, Pfizer Canada ULCInflammation and Immunology, Pfizer Canada ULCAbstract Introduction The safety of tofacitinib in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in clinical studies of ≤ 4 and 9.5 years, respectively. Post-marketing surveillance (PMS) data for tofacitinib from spontaneous and voluntary adverse event (AE) reports have been published for RA, but not PsA. To inform the real-world safety profile of tofacitinib in PsA, we evaluated AE reports submitted to the Pfizer safety database (including RA data for context). Methods Endpoints included AEs, serious AEs (SAEs), AEs of special interest (AESIs; serious infections, herpes zoster, cardiovascular events, malignancies, venous thromboembolism), and fatal cases. Exposure was estimated using IQVIA global commercial sales data. Number, frequency, and reporting rates (RRs; number of events/100 patient-years’ [PY] exposure) were summarized by indication and formulation (immediate release [IR] 5 or 10 mg twice daily], modified release [MR] 11 mg once daily, or all tofacitinib). The data-collection period differed by indication (PsA: 14 December 2017 [US approval, IR/MR] to 6 November 2021; RA: 6 November 2012 [US approval, IR] to 6 November 2021; MR approval, 24 February 2016). Results A total of 73,525 case reports were reviewed (PsA = 5394/RA = 68,131), with 20,706/439,370 PY (PsA/RA) of exposure. More AEs were reported for IR versus MR (IR/MR: PsA = 8349/7602; RA = 137,476/82,153). RRs for AEs (IR/MR: PsA = 59.6/113.4; RA = 44.0/64.8) and SAEs (PsA = 8.1/13.6; RA = 8.0/9.5) were higher with MR versus IR. AE RRs (RA) in the first 4 years after IR approval were 95.9 (IR; 49,439 PY) and 147.0 (MR; 2000 PY). Frequency of SAEs, AESIs, and fatal cases was mostly similar across formulations and indications. The most frequently-reported AE Preferred Terms (PsA/RA) included drug ineffective (20.0%/17.8%), pain (9.7%/10.6%), condition aggravated (9.9%/10.5%), headache (8.8%/7.9%) and, for PsA, off-label use (10.5%/3.4%). Conclusions Tofacitinib PMS safety data from submitted AE reports were consistent between PsA and RA, and aligned with its known safety profile. Exposure data (lower MR versus IR; estimation from commercial sales data), reporting bias, reporter identity, and regional differences in formulation use limit interpretation.https://doi.org/10.1007/s40744-023-00576-8Post-marketing surveillancePsoriatic arthritisRheumatoid arthritisSafetyTofacitinib |
| spellingShingle | Gerd R. Burmester Laura C. Coates Stanley B. Cohen Yoshiya Tanaka Ivana Vranic Edward Nagy Irina Lazariciu All-shine Chen Kenneth Kwok Lara Fallon Cassandra Kinch Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis Rheumatology and Therapy Post-marketing surveillance Psoriatic arthritis Rheumatoid arthritis Safety Tofacitinib |
| title | Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis |
| title_full | Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis |
| title_fullStr | Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis |
| title_full_unstemmed | Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis |
| title_short | Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis |
| title_sort | post marketing safety surveillance of tofacitinib over 9 years in patients with psoriatic arthritis and rheumatoid arthritis |
| topic | Post-marketing surveillance Psoriatic arthritis Rheumatoid arthritis Safety Tofacitinib |
| url | https://doi.org/10.1007/s40744-023-00576-8 |
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