Publications

Relationship between lymphocyte count and risk of infection in Japanese rheumatoid arthritis patients treated with tofacitinib

Modern Rheumatology 2024;34:1115–24 doi: 10.1093/mr/roae030

Tanaka Y,

Takeuchi T,

Valdez H,

Collinge M,

Zwillich SH,

Toyoizumi S,

Kwok K,

Hirose T

Tanaka et al. observed that in Japanese patients with rheumatoid arthritis treated with tofacitinib, those with absolute lymphocyte counts (ALCs) <0.5x10³ cells/mm³ had a higher risk of serious infections and herpes zoster events compared to patients with higher ALC levels. This threshold may help identify increased infection risk in this population

Keywords:

• Efficacy,
• Infections,
• JAK,
• MTX,
• Tofacitinib

Contributo di una variante prevalente in Europa vicino a CD83 e di una variante prevalente in Asia orientale vicino a IL17RB al rischio di herpes zoster nel trattamento con tofacitinib: risultati delle meta-analisi dello studio sull'associazione a livello di genoma

Arthritis Rheumatol. 2021;73(7):1155–66

Bing N,

Zhou H,

Chen X,

Hirose T,

Kochi Y,

Tsuchida Y,

Ishigaki K,

Sumitomo S,

Fujio K,

Zhang B,

Valdez H,

Vincent MS,

Martin D,

Clark JD.

Genetic analysis of tofacitinib-treated subjects with RA or PsO identified multiple loci associated with increased herpes zoster (HZ) risk.It is well known that HZ risk is elevated in subjects with RA compared with the general population, and that treatment with JAK inhibitors may result in increased risks compared with TNFi and other bDMARD treatments. To this end, Bing, et al. used genome-wide association studies to identify genetic factors associated with an increased risk/faster onset of HZ ...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections

Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data

Annals of the Rheumatic Diseases 05 August 2020 2020 Nov;79(11):1400-1413. doi: 10.1136/annrheumdis-2019-216761. Epub 2020 Aug 5.

Mease P,

Charles-Schoeman C,

Cohen S,

Fallon L,

Woolcott J,

Yun H,

Kremer J,

Greenberg J,

Malley W,

Onofrei A,

Kanik KS,

Graham D,

Wang C,

Connell C,

Valdez H,

Hauben M,

Hung E,

Madsen A,

Jones TV,

Curtis JR

Concerns surrounding increased rates of PE and cardiovascular associated deaths has led to black box warnings when prescribing JAK inhibitors. As such, ongoing investigations regarding cardiovascular and VTE event risks in JAK inhibitor therapies, both clinical and real-world, are vital. Mease and colleagues consider data from clinical tofacitinib development programmes, and the ongoing real-data study A3921133. Conclusions from data analysis state that those with pre-existing cardiovascular and...

Keywords:

• JAK,
• Tofacitinib,
• Safety

Long-term Effectiveness of Live Herpes Zoster Vaccine in Patients with Rheumatoid Arthritis Subsequently Treated with Tofacitinib

Ann Rheum Dis. 2020 10.1136/annrheumdis-2019-216566

Winthrop KL,

Wouters A,

Choy EH,

Chen C,

Biswas P,

Wang L,

Soma K,

Needle E,

Valdez H,

Rigby WFC

The results of ORAL Sequel suggest that the live zoster vaccine (LZV) may not provide adequate long-term protection in patients with RA receiving TOF. This LTE study enrolled 100 patients with RA, 14 weeks post LZV vaccination. Patients received either TOF 5 mg BID, or TOF 10 mg BID in addition to any background csDMARDs. Incidence rates and 95% CIs for HZ post-vaccination were calculated based on time to first event. Short-term varicella zoster vaccine (VZV) specific immunity was evaluated at ...

Keywords:

• JAK,
• Tofacitinib,
• Vaccination

Sicurezza ed Efficacia di Baricitinib nei Pazienti Trattati con Farmaci Antireumatici Modificanti la Malattia Sintetici Convenzionali o Corticosteroidi

Arthritis Rheumatol 2018 DOI: 10. 1002/art.40780

van Vollenhoven R,

Lee EB,

Strengholt S,

Mojcik C,

Valdez H,

Krishnaswami S,

Biswas P,

Lazariciu I,

Hazra A,

Clark JD,

Hodge J,

Wang L,

Choy E

Tofacitinib (TOF) treatment is associated with short-term transient increases in absolute lymphocyte counts (ALC), followed by a gradual decline to reach steady state by ~48 months. Changes in both ALC and lymphocyte subset counts (LSC) were reversible upon TOF discontinuation. Low ALC but not LSC were associated with an increased risk of serious infective episodes (SIEs) and herpes zoster (HZ). This data supported the treatment recommendations on ALC counts for starting and continuing therapy w...

Keywords:

• JAK,
• Tofacitinib,
• MOA

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

Arthritis Rheumatol 2017;69(10):1960–68

Winthrop KL,

Curtis JR,

Lindsey S,

Tanaka Y,

Yamaoka K,

Valdez H,

Hirose T,

Nduaka CI,

Wang L,

Mendelsohn AM,

Fan H,

Chen C,

Bananis E

The results of this analysis of patients with herpes zoster (HZ) within the global tofacitinib (TOF) RA programme suggest that there is likely to be a greater HZ risk in patients receiving TOF and glucocorticoids compared with patients receiving TOF monotherapy.The global TOF RA development programme comprised 2 Phase 1, 9 Phase 2, 6 Phase 3 and 2 long-term extension studies. These studies included 6192 patients; data were reviewed to identify cases of HZ. Crude incidence rates of number of pati...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections

Herpes Zoster and Tofacitinib Therapy in Patients with Rheumatoid Arthritis

Arthritis Rheumatol 2014;66:2675–84

Winthrop KL,

Yamanaka H,

Valdez H,

Mortensen E,

Chew R,

Krishnaswami S,

Kawabata T,

Riese R

Patients who were treated with tofacitinib in the RA clinical development programme were more likely to develop herpes zoster than were those who received placebo.Cases of herpes zoster reported by investigators in the Phase 2, Phase 3 and long-term extension studies of tofacitinib were evaluated. Herpes zoster was noted in 5% of tofacitinib-treated patients; only 7% of these cases were serious, no patients with herpes zoster died and only 10% permanently discontinued tofacitinib treatment.The o...

Keywords:

• JAK,
• Tofacitinib,
• Infections

Herpes Zoster and Tofacitinib Therapy in Patients with Rheumatoid Arthritis

Arthritis Rheumatol. 2014 Jun 18. [Epub ahead of print]

Winthrop KL,

Yamanaka H,

Valdez H,

et al.

It is well established that patients with RA are at an increased risk of herpes zoster (HZ). What is less well known is whether some of the newer therapies available for treatment of RA increase this risk. Tofacitinib has been reported to be associated with an increased risk of HZ and this study quantifies that risk and reviews potential factors that represent an increased risk. Using data from the tofacitinib RA development programme; phase 2, 3, and long-term extension clinical trials, over 20...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections