About

Katherine Nicole Theken is an Assistant Professor of Oral Surgery & Pharmacology at the University of Pennsylvania's Perelman School of Medicine. She is affiliated with the Department of Oral Surgery & Pharmacology and is part of the Pharmacology Graduate Group. Her role involves teaching and research within these fields, contributing to the academic and clinical missions of the institution.

Research topics

• Internal medicine
• Medicine
• Pharmacology
• Anesthesia

Selected publications

• Depression of tryptophan may contribute to adverse effects of naproxen

  Nature Communications · 2026-02-14

  articleOpen access

  Non-steroidal anti-inflammatory drugs are popular choices for the mitigation of pain and inflammation; however, they are accompanied by adverse effects in the gastrointestinal and cardiovascular systems. Identifying biomarkers and mechanisms for early gastrointestinal or cardiovascular disease detection is desirable. Here we compare the effects of placebo, naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase 2 inhibitor and find a decrease in tryptophan and kynurenine levels in the plasma of healthy volunteers who receive naproxen. We further validate this result in mice. Depression of tryptophan is independent of inhibition of either cyclooxygenase but rather, is due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescues fecal blood loss and inflammatory gene expression driven by IL-1β in the heart. Furthermore, tryptophan also rescues changes in genes that are reflective of inflammation and tissue damage in the gut. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been associated with adverse effects affecting both the cardiovascular and gastrointestinal systems. Here the authors show that NSAIDs lower plasma tryptophan concentrations in humans and mice and that replacement of tryptophan in mice treated with naproxen leads to decreased adverse effects.

  PublisherOA PDFDOI

• Age and the Diurnal Oscillatory Features of the Human Chronobiome

  medRxiv · 2026-01-23 · 2 citations

  article

  The molecular clock regulates diverse aspects of human biology. As people age, diurnal rhythms deteriorate, most evidently in the daytime napping and nighttime waking of older individuals. To understand how temporal deconsolidation of oscillatory networks could contribute to age-related disease expression, we studied the chronobiome at unprecedented depth in young and old apparently healthy individuals. Transomic integration segregated age groups and identified candidate mechanisms by which oscillatory function might contribute to age dependent distinctions. In an orthogonal approach, we validated as true cyclers many proteins identified in the UK Biobank as predictors of health and disease outcomes. Here, age-specific alterations in the cycling proteome across disease phenotypes is consistent with our hypothesis that deconsolidated circadian programs associate with increased susceptibility to age-related disease.

  PublisherDOI

• The Influence of Sex Hormones on Post-Operative Pain Following Third Molar Extraction

  Scholarly Commons (University of Pennsylvania) · 2025-09-11

  otherOpen accessSenior author

  This study investigated the relationship between sex hormones, post-operative pain, and opioid use following third molar extraction. Eighty-five healthy adults (48 women, 37 men; ages 18–37) provided baseline blood samples, which were analyzed for hormone levels using ELISA. Pain intensity was recorded on a 0–10 numeric scale during a 4-hour inpatient period. Patients received either ibuprofen or a placebo pill in a randomized, double-blind design once their pain reached a score of 4/10 or higher. Post-discharge, patients managed pain with scheduled ibuprofen and acetaminophen, and oxycodone was provided for breakthrough pain. While no statistically significant associations were identified between hormone levels and pain scores, women were more likely than men to use opioids, and preliminary trends suggested oral contraceptive users required fewer opioids than non-users. Hormone levels aligned with expected physiological patterns, confirming the reliability of the data and hormone assays. These findings highlight potential modulatory effects of sex hormones on pain perception and opioid use, warranting further investigation with larger cohorts.

  Publisher

• Minimum clinically important differences in acute pain: a patient-level re-analysis of randomized controlled analgesic trials submitted to the US Food and Drug Administration

  Pain · 2025-05-09 · 8 citations

  articleOpen access

  ABSTRACT: The lack of established minimum clinically important differences in acute pain has made it challenging to interpret efficacy in analgesic trials. We performed a patient-level re-analysis of double-blind, placebo-controlled trials submitted to the US Food and Drug Administration to estimate minimum clinically important differences in acute postoperative pain. Trials were categorized by acute surgical pain model: dental extraction, bunionectomy, orthopedic surgery, and soft tissue surgery. Pain intensity was assessed using the 0 to 10 numeric rating scale (NRS) or 0 to 100 visual analog scale, with visual analog scale scores converted to NRS for analysis. To avoid misclassification from arbitrary thresholds on global impression of change or pain relief scales, meaningful pain relief was determined using the double-stopwatch technique, where patients actively indicated the times they experienced perceptible and meaningful relief. Across 29 trials, 9047 patients with moderate-to-severe baseline pain were included. Patients with severe baseline pain (NRS ≥7) reported meaningful relief at a higher absolute NRS and required larger absolute reductions in pain intensity than those with moderate baseline pain (NRS 4-<7). However, the percent reduction in pain at meaningful relief remained stable across baseline pain levels, suggesting patients assess meaningful relief in relative rather than absolute terms. No appreciable differences in the changes in pain at meaningful relief were observed by age, sex, drug, or route of administration. Receiver operating characteristic curve analysis identified a 50% reduction in pain intensity as a consistent and clinically meaningful threshold across surgical pain models, supporting its use as a standardized patient-centric metric for evaluating analgesic efficacy.

  PublisherOA PDFDOI

• Predictors of response to full agonist opioids in enriched enrollment randomized withdrawal clinical trials: a participant-level data meta-analysis

  Pain · 2025-09-02 · 1 citations

  article

  ABSTRACT: This study aims to identify predictors of success in treating chronic pain patients with full agonist opioids by analyzing harmonized individual patient data from 5594 participants in 9 enriched enrollment randomized withdrawal clinical trials available in the Food and Drug Administration data repository. We analyzed both the participants' success with titration and continued success in the 84-day maintenance phases after randomization for those maintained on the drug. We used the full data set to assess participant demographics and subsets of data containing participant reported outcomes at baseline. Participants had an average age of 51, with 55% female participants and 66% non-Hispanic white. No clinically relevant differences were observed between participants who failed titration or those who continued on full agonists through the maintenance phase. Prediction models were developed using mixed effects logistic regression and generalized linear mixed models, with the study as a random effect to account for inter-study differences. Despite large numbers, the analysis did not reveal clinically useful prediction models for either the titration or maintenance phase; however, higher initial pain scores were modest predictors of poorer outcomes. No patient-reported outcome measures were predictive of responses to therapy. The study's limitations include its volunteer-based sample and the exclusion criteria, although excluding patients with opioid use disorder or serious psychological conditions are similar to those used in clinical care. As no strong predictive factors for successful treatment were identified, the decision to use opioids to treat chronic pain requires careful clinical judgment and close monitoring.

  PublisherDOI

• Predictors of successful initiation of buprenorphine in enriched enrollment randomized withdrawal clinical trials in both opioid experienced and naïve participants: a participant-level meta-analysis

  PAIN Reports · 2025-06-05

  articleOpen access

  Introduction: No prediction models exist for the success for buprenorphine initiation in opioid-naïve patients or in transition from other opioids in patients treated for chronic pain. Objectives: To create a prediction model for the successful use of buprenorphine to treat chronic pain. Methods: Stepwise Akaike information criterion prediction modeling procedures were applied to a harmonized participant-level data set of 10 enriched enrollment randomized withdrawal clinical trials of buprenorphine submitted to the Food and Drug Administration. Available baseline factors and nine patient-reported outcomes were considered to predict success with the titration (10 studies) and maintenance of benefit after randomization (5 studies). Patient-reported outcomes were modeled separately given inconsistent use across studies. Results: No prediction model reached an area under the receiver operator curve ≥0.70, the threshold for clinical usefulness. Successful initiation or transition of buprenorphine was accomplished in 3541 of 6052 (58.7%) participants, and 614 of 877 (70.0%) completed the 12-week maintenance phase with no difference between opioid-experienced and opioid-naïve participants. Only a medical history of obesity and baseline pain were retained in the overall titration model and only baseline pain in the maintenance model. Only brief pain inventory and subject opioid withdrawal scores were retained in the titration subsets containing those measures. Conclusion: No clinically useful prediction models of clinical benefit were identified, but a few covariates may be of interest in future studies of the initiation of buprenorphine in opioid-naïve patients or of transition from other opioids to buprenorphine. The lack of a predictor supports considering a trial of buprenorphine in clinically relevant scenarios for patients without known opioid use disorder, including careful monitoring and an a priori plan to deal with any problems that may occur.

  PublisherDOI

• Group Response Analysis: Clinically Interpretable Longitudinal Responder Analysis Methods Developed Using FDA Data

  medRxiv · 2025-08-15

  preprintOpen access

  1 Abstract Responder analyses for the evaluation of randomized clinical trial (RCT) data have become more common in the recent past, since they can provide the medical community with results that are more directly applicable to clinical care. For pain studies, the predominant responder analysis compares the change in the individual participants’ pain level at baseline to their value at the end of the study period and uses a predetermined clinically important change cut-off value to define a response. While useful, this method substantially reduces the efficiency of the RCT by dichotomizing the results and is limited to comparing the baseline to the end of the study only. In this paper, we introduce a novel approach to the patient response over time with a focus on single dose post-operative studies. This technique provides graphical presentations and statistical approaches to understand the onset of any specified level of response, the maximum proportion of patients with a response at any point in time, and the duration of that response over time. In addition, each outcome can be summarized to examine the result across all possible cut-off points for clinically important differences (CID). We accomplish this by introducing three interrelated, longitudinal efficacy statistics: ROOT, GRO, and GROOT. The response outcome over time (ROOT) estimates the total proportion of a study period an individual patient spends as a responder. The group response outcome (GRO) estimates the instantaneous proportion of responders at all time points across the study period. The group response outcome over time (GROOT) summarizes total efficacy in a cohort, and can be calculated as the area under the GRO curve, or as the mean ROOT; they are identical. This novel method provides a clinically interpretable responder analysis over the full period of the study and, by using every data point across time, mitigates the loss of statistical power typically associated with dichotomized responder outcomes. Group response analysis is based upon repeated assessments of categorical or continuous measures categorizing each participant’s status as a treatment responder or non-responder at every timepoint based on the prespecified clinically important difference. Both the visual and statistical comparison of any two or more curves provide a comparison of the overall efficacy, which can be statistically tested using a standard asymptotic hypothesis test (such as Wald (Johnson &amp; Romer, 2016)). The method allows for an integrated evaluation of three main components of drug efficacy: the proportion of participants achieving a CID over time (effect), the time to achieve that response (onset), and the length of the response (duration). In this paper, we present the group response analysis methodology and then illustrate it using data from a placebo-controlled randomized clinical trial (RCT) for postoperative pain after third molar extraction treated with meloxicam and ibuprofen as an active comparator (Christensen et al., 2018). Our approach yields similar effect sizes as the sum of pain intensity differences (SPID) commonly used for pain study analyses while providing superior clinical interpretability and a more complete evaluation of drug therapies beyond just efficacy. We propose that this method can be used as a primary or secondary analysis of pain RCTs to answer the question of the patient response to treatment and provide suitable data to compare efficacies across treatment groups.

  PublisherOA PDFDOI

• Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response

  Hypertension · 2025-12-29 · 1 citations

  articleOpen access1st authorCorresponding

  BACKGROUND: Large clinical trials compared distinct nonsteroidal anti-inflammatory drugs in terms of their risk of adverse cardiovascular events. However, whether pharmacologically equipotent doses were used, that is, whether a similar degree of COX (cyclooxygenase)-2 inhibition was achieved, was not considered. We compared drug target inhibition and blood pressure (BP) response to celecoxib and naproxen. METHODS: Sixteen healthy participants were treated with celecoxib (200 mg/d), naproxen (500 mg/d), or placebo for 7 days in a double-blind, crossover design. The degree of COX inhibition was assessed ex vivo using established whole blood assays and in vivo by quantifying urinary metabolites of thromboxane A 2 (COX-1) and prostacyclin (COX-2). Ambulatory BP was measured throughout the final dosing interval. RESULTS: Both nonsteroidal anti-inflammatory drugs inhibited COX-2 activity relative to placebo, but naproxen inhibited COX-2 activity to a greater degree (62.9±21.7%) than celecoxib (35.7±25.2%; P &lt;0.05). Similarly, naproxen treatment inhibited prostacyclin formation in vivo (48.0±24.9%) to a greater degree than celecoxib (26.7±24.6%; P &lt;0.05). Naproxen significantly increased BP compared with celecoxib (mean arterial pressure, +2.5 [95% CI, 1.5–3.5] mm Hg; systolic BP, +4.0 [95% CI, 2.9–5.1] mm Hg; and diastolic BP, +1.8 [95% CI, 0.8–2.8] mm Hg; P &lt;0.05 for all). The difference in systolic BP relative to placebo was associated with the degree of COX-2 inhibition ( P &lt;0.05). CONCLUSIONS: Future studies should consider pharmacokinetic and pharmacodynamic properties, as well as patient-specific factors that may modulate the cardiovascular risk of nonsteroidal anti-inflammatory drug use. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02502006.

  PublisherOA PDFDOI

• Do infectious disease consultations improve outcomes of surgical management of MRONJ?

  Oral Surgery Oral Medicine Oral Pathology and Oral Radiology · 2025-01-05 · 1 citations

  article
  PublisherDOI

• Predictors of Supplemental Opioid Use After Third Molar Extraction

  medRxiv · 2025-07-18

  preprintOpen accessSenior authorCorresponding

  Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line analgesics following third molar extraction, but some patients require supplemental opioids for pain management. The objective of this study was to identify demographic and clinical factors that predicted supplemental opioid use following third molar extraction in patients treated with an evidence-based analgesic regimen. Methods: Healthy adults underwent surgical extraction of partial or full bony impacted mandibular third molar. When pain intensity was ≥4/10, participants were given ibuprofen 400 mg (N=59) or placebo (N=26) in a randomized, double-blind design. After 4h, all participants transitioned to open-label ibuprofen 400 mg + acetaminophen 500 mg, with oxycodone 5 mg available for breakthrough pain. Analgesic use was documented for the first week after extraction. Predictors of supplemental opioid use in addition to ibuprofen + acetaminophen were evaluated by logistic regression. Results: Ibuprofen + acetaminophen provided adequate analgesia in most of the 85 participants, with 17 participants (20%) using supplemental oxycodone in the first week after extraction. Female sex (OR: 6.770; 95% CI: 1.657-35.57; p=0.013) and higher body mass index (BMI) (OR: 1.253; 95% CI: 1.052-1.525; p=0.016) were associated with increased odds of supplemental opioid use, while higher difficulty index (Pederson score) slightly decreased the odds of supplemental opioid use (OR: 0.852; 95% CI: 0.724-0.993; p=0.043). Adding pre-surgery neutrophil counts improved model fit, with higher neutrophil counts associated with lower odds of supplemental opioid use (OR: 0.435; 95% CI: 0.212-0.775; p=0.011). Conclusions: Female sex, higher BMI, and pre-surgery neutrophil counts were predictors of supplemental opioid use in patients treated with an evidence-based analgesic regimen. Greater surgical difficulty of third molar extraction does not increase the likelihood of supplemental opioid use.

  PublisherOA PDFDOI

Frequent coauthors

• Garret A. FitzGerald

  Translational Therapeutics (United States)

  40 shared

• Shaon Sengupta

  Children's Hospital of Philadelphia

  28 shared

• Soon Yew Tang

  California University of Pennsylvania

  25 shared

• Tilo Großer

  Bielefeld University

  23 shared

• Craig R. Lee

  University of North Carolina at Chapel Hill

  19 shared

• Nicholas F. Lahens

  Translational Therapeutics (United States)

  19 shared

• Elliot V. Hersh

  12 shared

• Darryl C. Zeldin

  National Institute of Environmental Health Sciences

  11 shared

Education

• Ph.D., Pharmaceutical Sciences

  University of North Carolina at Chapel Hill

  2011

• Pharm.D., Pharmacy

  University of Pittsburgh

  2006