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Background Pain, morning stiffness and disease activity are core domains of ankylosing spondylitis (AS), relevant to patients (pts) and physicians. AS treatment guidelines recommend using the AS Disease Activity Score C-reactive protein (ASDASCRP) to assess disease activity. Greater improvements in pain, morning stiffness and disease activity were previously shown with tofacitinib vs placebo (PBO) in pts with AS.[1] There are limited data on time to improvement in these core domains in pts with AS receiving tofacitinib.
Objectives To estimate the median time to improvement of pain, morning stiffness and disease activity in tofacitinib-treated pts with AS.
Methods This post hoc analysis used data from a Phase 3 trial (NCT03502616)[1] in pts with AS receiving tofacitinib 5 mg twice daily (BID) or PBO to Week (W)16. After W16, all pts received open-label tofacitinib 5 mg BID to W48. Outcomes included nocturnal pain (numerical rating scale 0–10), morning stiffness (mean of Bath AS Disease Activity Index [BASDAI] Questions 5 and 6), BASDAI total score and ASDASCRP. Median time (weeks) to initial improvement events was estimated using non-parametric Kaplan-Meier models. Initial improvement event was defined as time to first post-baseline observation with an improvement of ≥30% (nocturnal pain [“much improved”][2]), ≥50% (nocturnal pain [“very much improved”],[2] morning stiffness and BASDAI total score) or ASDASCRP ≥1.1 (clinically important improvement)/≥2.0 (major improvement) points.
Results Overall, 269 pts (tofacitinib: n=133; PBO→tofacitinib: n=136) were assessed. Median times to initial improvement events were shorter with tofacitinib vs PBO→tofacitinib (p<0.05 [Table 1]). Median times to initial ≥30% and ≥50% improvement in nocturnal pain for tofacitinib were 4 and 8 weeks, respectively, and 24 weeks (8 weeks since switch to tofacitinib) for both thresholds for PBO→tofacitinib. Median time to initial ≥50% improvement in morning stiffness and BASDAI total score for tofacitinib was 12 weeks, and 32 weeks (16 weeks since switch to tofacitinib) for PBO→tofacitinib. Median time to ASDASCRP improvement ≥1.1 for tofacitinib was 4 weeks, and 24 weeks for PBO→tofacitinib (not estimable [NE] for ASDASCRP improvement ≥2.0 [both treatment arms]). Limitations: this was a post hoc analysis, there was no active treatment comparator, trial pt population may not reflect routine care pt population and comparisons with PBO were only possible to W16.
| Median time (interquartile range) | |||
|---|---|---|---|
| Improvement threshold | Tofacitinib 5 mg BID (N=133) | PBO→tofacitiniba (N=136) | p value |
| ≥30% improvement | |||
| Nocturnal pain | 4 (2–24) | 24 (8–32) | 0.0003 |
| ≥50% improvement | |||
| Nocturnal pain | 8 (4–40) | 24 (16–NE) | <0.0001 |
| Morning stiffness | 12 (4–NE) | 32 (24–NE) | 0.0091 |
| BASDAI total score | 12 (4–NE) | 32 (16–NE) | 0.0002 |
| Improvement in ASDASCRP | |||
| ≥1.1 points | 4 (2–20) | 24 (12–40) | <0.0001 |
| ≥2.0 points | NE | NE | 0.0361 |
p values are based on log-rank tests for differences in survival curves for tofacitinib vs PBO→tofacitinib
aSwitched to open-label tofacitinib at W16
Conclusion In pts with AS, during the first month of tofacitinib treatment, it is expected that half of pts will experience ≥30% improvement in nocturnal pain (“much improved”) and a clinically important improvement in ASDASCRP. During the first 2 and 3 months of tofacitinib treatment, it is expected that half of pts will experience ≥50% improvement in nocturnal pain (“very much improved”) and morning stiffness, respectively. Improvements in pain, morning stiffness and disease activity occurred more rapidly with tofacitinib vs PBO→tofacitinib. This study informs physicians and pts receiving tofacitinib of when improvement in these core domains in AS may be anticipated.
References
[1] Deodhar et al. Ann Rheum Dis 2021; 80: 1004-13
[2] Dworkin et al. J Pain 2008; 9: 105-21
Acknowledgements This study was sponsored by Pfizer. Medical writing support, under the direction of the authors, was provided by Chimwemwe Chibambo, MBChB, CMC Connect, a division of IPG Health Medical Communications, and was funded by Pfizer, New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022; 175: 1298-1304).
Disclosure of Interests Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc and UCB, Consultant of: AbbVie, Eli Lilly, Janssen, MoonLake, MSD, Pfizer Inc and UCB, Grant/research support from: AbbVie and Novartis, Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc and UCB, Rachid Bahiri: None declared, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cassandra Kinch Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jihane Rammaoui Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.
Keywords: Pain, Patient reported outcomes, Spondyloarthritis
DOI: 10.1136/annrheumdis-2023-eular.2417