The Dental Status of Patients Taking Common Biologic Agents: A Single‐Center Cross‐Sectional Study

ABSTRACT

Objectives

Despite expanding use and medical applications, little is known about the impact of biologic agents (BAs) on dental treatment. The aim of this study was to investigate the dental status of patients on common classes of BAs to understand treatment needs and use in this population.

Methods

A retrospective cross‐sectional study was conducted on patients treated with the most common classes of BA (tumor necrosis factor‐alpha [TNF‐α] inhibitors, interleukin (IL) inhibitors, and lymphocyte modulators) from 1/7/2017 to 1/7/2022. Data on demographic factors, BA treatment, medical conditions including indication, restorative and periodontal treatments, and decayed, missing, and filled tooth index (DMFT) were compared descriptively.

Results

The study identified 247 patients treated with 24 different BAs. Restorative and periodontal treatment was completed on 60.3% and 72.9% of patients, respectively. The DMFT scores were higher in the study cohort compared to the average US adult population. The analysis revealed an upward trend in both periodontal and restorative treatments.

Conclusions

This study provides the first comprehensive characterization of the oral health status and treatment needs of patients taking BAs. The findings suggest a higher dental treatment burden in this population, particularly regarding restorative care in this population, a finding that may be confirmed or expanded in future evaluations.

1. Introduction

A biologic agent (BA) is defined by the National Cancer Institute as “a substance that is made from a living organism or its products and is used in the prevention, diagnosis, or treatment of cancer and other diseases” (National Cancer Institute n.d.). BAs primarily consist of monoclonal antibodies and variant fusion proteins. Monoclonal antibodies are proteins formulated to react with target antigens, while variant fusion proteins are created by combining separate genes isolated from one or more living things (Chong and Wong 2007; National Cancer Institute n.d.). BAs are named according to their source (Farah et al. 2019).

Various BAs are used across specialties of medicine, including oral medicine, to treat malignant, autoimmune, and inflammatory conditions, including Sjogren's syndrome and pemphigus vulgaris (Alaibac 2019; Gueiros et al. 2019; O'Neill and Scully 2013). Biologics such as tumor necrosis factor‐alpha (TNF‐α) inhibitors reduce inflammation and other pathologic processes through modulation of inflammatory and immunologic pathways (Abunemer et al. 2023). The systemic side effects of BAs have been well characterized and include an increased rate of malignancy, new or recurrent infection, and infusion reactions (Patel and Khan 2017). For example, BAs have been linked to the reactivation of tuberculosis, hepatitis B, and herpesviruses (Koo et al. 2011). Due to these risks, pretreatment evaluation of patients is essential for appropriate case selection and preparation. This process is focused on determining the patient's overall health status, including untreated infection, uncontrolled heart failure, untreated comorbid autoimmune processes, or other comorbidities that may be exacerbated during treatment (Findeisen et al. 2021; O'Neill and Scully 2012a).

While the systemic effects of these medications have been well characterized, the oral impacts of BAs remain minimally studied. Evidence to date identifies some adverse effects in the oral cavity of patients taking BAs and has theorized about the effects of BAs on healing and inflammatory conditions in the mouth (France et al. 2023; Georgakopoulou and Scully 2015; O'Neill and Scully 2012b). This data includes evidence of developing allergic reactions, lichenoid inflammation, medication‐related osteonecrosis of the jaw (MRONJ), and certain malignancies while in treatment with BAs. MRONJ, in particular, has been noted in case reports of patients treated with TNF‐α antagonists and lymphocyte modulators (Cassoni et al. 2016; Favia et al. 2017; Javelot et al. 2020). Development of MRONJ is theorized as a risk of these agents due to reduced receptor activator of nuclear factor‐kB ligand (RANKL) levels during treatment with TNF‐alpha antagonists (Dhami and Culshaw 2022). As in medical contexts, other manifestations of delayed and incomplete healing have been posited during treatment with these agents, with little direct evidence existing in the literature. However, there has been minimal investigation regarding the dental treatment experience of this population, including the needs for restorative or periodontal treatment in patients taking BAs, or the tolerability of this treatment.

Some existing literature does postulate an impact of BAs on periodontal status. In addition to theoretical concerns, this includes some experimental evidence of the impact of these agents on a variety of periodontal disease markers. There are similarities between the inflammatory tissue destruction involved in systemic processes targeted by BAs and the inflammatory processes of periodontal disease (Dubey and Mittal 2020). It has long been established that interferon (INF)‐a and TNF‐α, due to their role in proinflammatory signaling and their inhibition of bone remodeling, contribute to the development and exacerbation of periodontal disease (Graves and Cochran 2003). An early primate study also provided evidence that anti‐TNF and anti‐interleukin (IL) agents can facilitate healing (Zhang et al. 2004). Therefore, when a patient receives anti‐TNF‐α agents, multiple studies have hypothesized that there may be a beneficial treatment effect on periodontal disease status (Kobayashi et al. 2014). Indeed, positive periodontal effects such as decreases in gingival index, bleeding on probing (BOP), and probing depths (PD) in these populations have been recorded (Posada‐López et al. 2022), and a systematic review examining the relationship between PD and BAs suggested improved healing (Peddis et al. 2019). Evidence from animal studies has also demonstrated reduced loss of connective tissue attachment, alveolar bone height, as well as reduced periodontal inflammation through inhibition of interleukin (IL)‐1 (Delima et al. 2001, 2002). However, some studies demonstrate that there may be a negative impact on some periodontal disease parameters such as gingival inflammation due to the inhibition of immune system factors (Pers et al. 2008). While much of the evidence points toward a positive association between periodontal health and biologic medications, there is still limited knowledge regarding the lived experience of periodontal disease and the treatment experience in patients who are using BAs.

Dental caries is a complex multifactorial bacterial infection related to oral microbiome dysbiosis and biofilm propagation (Pitts et al. 2021). Development of caries depends on an interplay between a susceptible host, pathogenic bacteria, and a cariogenic substrate (Loesche 1986). Systemically, in addition to reactivation of latent infections as described above, the use of BAs has been found to trigger bacterial infections, such as the development of gastrointestinal infections, upper airway infections, and osteomyelitis (Bielory 2022; Georgakopoulou and Scully 2015). Orofacial osteomyelitis has repeatedly been identified as a complication in patients taking BAs, including in a case series of multiple patients taking infliximab who developed osteomyelitis after dental extraction (Bielory 2022; Ciantar and Adlam 2007). Infliximab is theorized to contribute to this complication through suppression of TNF‐α, in turn limiting granuloma formation and macrophage‐induced pathogen elimination. In patients taking infliximab, then, the oral cavity may contain a bacterial overabundance that can lead to local or systemic disturbances (Ciantar and Adlam 2007). A severe infection affecting the orofacial region, osteomyelitis development may be a risk in patients taking BAs and has been identified in this population (Sri et al. 2007; Tsuchiya et al. 2016). However, the data on bacterial infections in this patient population to date include limited information on other orofacial infections, do not include systematic studies regarding oral and maxillofacial risks in patients taking BAs, and do not include any data on caries rates or treatment experience.

In dental medicine, although review papers and case studies have hypothesized about disease or treatment‐related concerns for patients on BAs, there is a lack of patient data illustrating lived experience. In contrast to systemic side effects of BAs, which have been well characterized, oral impacts of these agents remain relatively unknown. Thus, more information on the dental status and treatment experience of patients taking BAs is needed. This study presents a first investigation of the dental and periodontal status of patients taking BAs via treatment needs of patients taking the three most common classes of BAs (Burmester 2024).

2. Methods

2.1. Study Set‐Up

To assess the oral health of patients receiving BAs, we conducted a retrospective cross‐sectional study using data from patients who were treated at the University of Pennsylvania School of Dental Medicine (Philadelphia, PA) between July 1, 2017 and July 1, 2022. The study was approved by the Institutional Review Board (IRB) as exempt (IRB Confirmation Number: 851121). We collected data on patients aged 18–90 years who had sufficient dental records and were undergoing treatment with one of the three most common classes of BAs: TNF‐α inhibitors, IL inhibitors, and lymphocyte modulators. These patients were identified by querying the electronic health record (EHR) system (axiUm, Exan, Las Vegas, NV) for the presence of medications in these categories. A comprehensive list of the specific medications searched, including both brand and generic names, is provided in Appendix A. The study period began on July 1, 2017, coinciding with the initiation of the axiUm EHR system at our institution and continued for 5 years.

We excluded patients who were younger than 18 or older than 90 years and any dental treatment received prior to starting BA therapy. Importantly, we included patients regardless of how long they had been on BA treatment, even if they had discontinued or switched BAs. This approach was based on the assumption that the effects of BAs on oral health may persist even after treatment ends.

2.2. Baseline Data

For eligible patients, we collected demographic data, including birth year, sex (male, female, unknown, or other), treatment level (predoctoral, postdoctoral, or independent provider), and years of active treatment. Year of birth was used instead of age to standardize comparisons between patients treated in different years and for different periods of time. In addition, we recorded details about the specific BAs patients were taking, including the BA class, the reason for treatment, the date the treatment began (if it was after the patient's first dental visit), and any other relevant medical conditions or medications.

2.3. Dental Treatment Received

Information gathered on restorative dental treatment included the number and types of restorations (e.g., anterior or posterior restorations, crowns, inlays, onlays) performed each year, as well as the diagnoses associated with those procedures. We also recorded the decayed, missing, and filled tooth (DMFT) index for each patient. Decayed, missing, and filled teeth were totaled across the entire study population (“Total Cohort”) and for patients who received restorative treatment (“Restorative Patients”). These groups were compared to existing data on the DMFT status of adult patients in the US according to the US Centers for Disease Control and Prevention (CDC) Oral Health Surveillance report from 2011 to 2016 (Lin et al. 2019), the most recent data available. DMFT scores across these three groups were compared using paired t‐tests with significance set at p = 0.05. For periodontal treatments, we documented the frequency of prophylaxes, scaling and root planing (SRP), periodontal surgeries, and other procedures (e.g., bone grafts, implants, re‐evaluations). Additionally, oral medicine evaluations, extractions, and other dental care received during the study period were recorded. Since dental prostheses can be created for various reasons, we grouped them with other treatments rendered. For all procedures, data collection focused on treatments performed as surrogates for need, given the limits of retrospective evaluation.

We also completed a subanalysis of restorative treatment completed for patients taking the most common BAs in our dataset, defined as medications prescribed to more than 10 patients in the cohort. For these agents, we compared the restorative treatment experiences within and across medications. This included the total number of patients receiving restorative treatments per year (2017–2022), the number of restorations, and the types of restorations. We also calculated the percentage of patients on a particular BA who received restorative treatments in each year relative to the total number of patients who received any restorative treatments that year. Given the small sample sizes for most BAs, statistical comparisons across agents were not feasible, so all comparisons were made descriptively.

2.4. Data Management and Analysis

Data extraction was completed using a secure form developed by the senior investigator (K.F.α), with input from three additional investigators (N.V., S.S., N.M.). The form was regularly reviewed and edited during data collection, and a formal review was conducted once 10% of the data was complete. One investigator (N.V., S.S., or N.M.) extracted the data for each chart, with validation by the senior investigator. To ensure consistency, we performed internal calibration by cross‐checking entries for the first 10% of charts and reviewing any discrepancies as they arose. After completing the data collection, three investigators (K.F., N.V., S.S.) cross‐checked each patient's chart to verify accuracy.

We analyzed the data descriptively and comparatively using secure Microsoft Excel workbooks. Demographic and treatment data were compiled for the entire cohort and compared across groups that received restorative and periodontal treatments during the study period. We specifically analyzed the frequency of restorative and periodontal treatments per year, broken down by treatment type and BA class. In all time‐based analyses, we accounted for the study period, including the effects of the 3‐month closure of our institution in 2020 due to the COVID‐19 pandemic, during which routine treatments were not performed.

3. Results

Our study identified and evaluated 247 eligible patients (152 females, 94 males, and 1 transgender patient) treated with 24 different BAs with an average birth year of 1969 (range: 1934–1998, Table 1). Patients were receiving BAs for a variety of conditions, as illustrated in Table 2. Four patients were treated with BAs for two disease indications. Twelve patients were treated with multiple agents during the study period. The following estimates are calculated according to the total number of agents used. Across our population, adalimumab (Humira) was the most prevalent BA, followed by etanercept (Enbrel) and infliximab (Remicade). TNF‐α inhibitors were the most common class of BAs in our population, accounting for 59.7% (n = 151 agents) of medications. No complications after treatment, including delayed healing, postoperative infections, or MRONJ, were identified in the patients studied.

TABLE 1.

Demographic features of study population including patient factors, biologic agent treatment, and disease targeted.

Age	Mean ± standard deviation	Range
Year of birth	1969 ± 16	1934–1998
Sex	n	Percent
Female	153	61.7%
Male	94	37.9%
Transgender/unknown	1	0.4%
Active patients	n	Months of data included
2017	109	6
2018	131	12
2019	148	12
2020	123	9
2021	141	12
2022	118	6
Medication class	n	Percent a
TNF inhibitor	151	59.7%
Interleukin inhibitor	75	29.6%
Lymphocyte modulator	27	10.7%
Class of disease being treated	n	Percent
Arthritis	115	46.4%
Colitis	48	19.4%
Dermatologic	28	11.3%
Unknown	27	10.9%
Other b	30	12.1%

^a Percentages calculated as the fraction of medications in listed class compared to all classes taken (247 patients taking 253 classes of medications).

^b Includes rheumatologic, neurologic, pulmonary, ENT, oncologic, and patients treated for multiple conditions.

TABLE 2.

Patient distribution by biologic agent and disease targeted including number and percent of patients in each category.

Biologic agent	n	Percent (%) a	Specific disease being treated	n	Percent (%) b
Humira (adalimumab)	78	29.8	Arthritis, not otherwise specified	44	17.5
Remicade (infliximab)	33	12.6	Rheumatoid arthritis	44	17.5
Enbrel (etanercept)	32	12.2	Crohn's disease	29	11.5
Dupixent (dupilumab)	22	8.4	Unknown	27	10.7
Stelara (ustekinumab)	18	6.9	Psoriasis	18	7.1
Rituxan (rituximab)	13	5.0	Psoriatic arthritis	15	6.0
Taltz (ixekizumab)	9	3.4	Colitis, not otherwise specified	13	5.2
Cosentyx (secukinumab)	7	2.7	Ankylosing spondylitis	10	4.0
Simponi (golimumab)	7	2.7	Asthma	9	3.6
Cimzia (certolizumab pegol)	6	2.3	Eczema	6	2.4
Actemra (tocilizumab)	6	2.3	Ulcerative colitis	6	2.4
Darzalex (daratumumab)	4	1.5	Inflammatory arthritis	4	1.6
Fasenra (benralizumab)	4	1.5	Multiple myeloma	3	1.2
Orencia (abatacept)	4	1.5	Dermatomyositis	2	0.8
Benlysta (belimumab)	3	1.1	Non‐Hodgkin's lymphoma	2	0.8
Nucala (mepolizumab)	3	1.1	Pemphigoid	2	0.8
Skyrizi (risankizumab)	3	1.1	Sinusitis	2	0.8
Tremfya (guselkumab)	3	1.1	Systemic lupus erythematosus	2	0.8
Arcalyst (rilonacept)	2	0.8	Atopic dermatitis	1	0.4
Gazyva (obinutuzumab)	1	0.4	Autoimmunity to progesterone	1	0.4
Ilumya (tildrakizumab‐asmn)	1	0.4	Behcet's disease	1	0.4
Kineret (anakinra)	1	0.4	Churg‐Strauss disease	1	0.4
Lemtrada (alemtuzumab)	1	0.4	Granulomatitis with polyangitis	1	0.4
Nulojix (belatacept)	1	0.4	Hidradenitis suppurativa	1	0.4
			Kidney transplant	1	0.4
			Lobular panniculitis with granuloma	1	0.4
			Muckle–Wells syndrome	1	0.4
			Multiple sclerosis	1	0.4
			Neuromyelitis optica	1	0.4
			Sarcoidosis	1	0.4
			Stills sisease	1	0.4
			Takayasu's arteritis	1	0.4

^a Percentages calculated compared to all medications taken by patients evaluated (262 medications).

^b Percentages calculated out of 252 disease indications being treated.

Periodontal treatment (prophylaxis, periodontal maintenance, SRP, periodontal surgery, or other periodontal treatment) was completed on 184 patients, which represents 72.9% of our patient population. All treatment categories were represented. “Other” periodontal treatments included implants, bone grafts, and periodontal re‐evaluation. Of the patients in this cohort who received periodontal treatment, 58.7% were taking TNF‐α inhibitors, 32.6% IL inhibitors, and 11.41% lymphocyte modulators. The distribution was 42.4% female (n = 78) and 28.3α% male (n = 52) with an average birth year of 1970. All biologic medications in our population except alemtuzumab (Lemtrada) and anakinra (Kineret) were represented in periodontal treatments. The majority of treatments were prophylaxis (271). Details of treatments administered are available as Figure 1A.

FIGURE 1.

Periodontal treatment experience of patients taking common biologic agents. (A) periodontal treatment experience by procedure. (B) Percent of active patients receiving periodontal treatment per year illustrating uptake of recommended oral health maintenance in this population. (C) number of procedures completed over time as a function of both number of active patients and months of data available for analysis with trend line showing overall increase in treatment delivered despite a decrease in 2020.

Periodontal patients were further categorized according to the nature of their treatments. The number of patients who received periodontal treatment indicative of periodontal disease (SRP or periodontal maintenance) was 78 (31.5% of all patients or 42.4% of patients who underwent periodontal care). The number of patients who only had prophylaxis treatment as routine maintenance without evidence of periodontal disease was 95 (38.4% of total patients or 51.6% of patients who underwent periodontal care). These patients are believed to represent those with gingivitis only, given that no more involved treatment was recommended. An additional 11 (4.45% of total patients or 5.98% of patients who underwent periodontal care) received only periodontal surgery and no preventive periodontal health maintenance. The number of periodontal procedures completed per month across the study period showed a general upward trend (Figure 1B) with a notable decrease during 2020. This accounts for a decrease in both preventive and active care during the COVID‐19 pandemic and remains despite calculations accounting for 3 months during which our institution delivered emergency care only. Procedures completed showed an overall upward trend as well over time, despite a decrease in procedures completed during 2020, even when controlling for time using months of treatment included in our data set each year (Figure 1C, slope = 0.0099, R ² = 0.80).

One hundred forty‐nine patients received restorative treatment, which represents 60.3% of the entire cohort. This subset was 55.0% female (n = 82), 44.3% male (n = 66), and 0.67% transgender (n = 1) with an average year of birth of 1969. Of the restorative patient population, 91 patients were treated with TNF‐α inhibitors (59.7% of the population), 46 patients (30.9%) were treated with IL inhibitors, and 16 patients (12.1%) were treated with lymphocyte modulators. Four restorative patients were taking both TNF‐α inhibitors and IL inhibitors during the study period. The most common BAs were adalimumab (Humira) in 46 patients, etanercept (Enbrel) in 23 patients, and infliximab (Remicade) in 19 patients. Restorative patients were taking all BAs represented in the total study population with the exception of tildrakizumab‐asmn (Ilumya) and alemtuzumab (Lemtrada).

Across all patients, 620 restorative procedures were completed, representing all classes. Restorative procedures not otherwise classified (“other”) included core build‐up restorations, posts, crown re‐cementations, and protective restorations. Anterior and posterior restorations were the most commonly performed procedures, with 150 anterior restorations and 285 posterior restorations completed (Figure 2A). The percentage of patients in active treatment receiving restorations varied from 31% to 36% from 2018 to 2022 after increasing from 23% in 2017 (Figure 2B). When controlling for variations in months of data included, the patient restoration treatment experience shows an upward trend across the years studied (Figure 2C, slope = 1.33, R ² = 0.84).

FIGURE 2.

Restorative treatment experience of patients taking biologic agents. (A) Distribution of restorative procedures completed over study period. (B) Percent of all active patients taking biologic agents who received restorative treatment per year illustrating a stable to increasing rate of restorative needs. (C) Restorations completed over time as a function of months of treatment data included with a stable to upward trend despite a consistent rate of patients treated.

DMFT scores were calculated for both the entire study cohort and for restorative patients specifically. The latter group of patients provides a better estimate of those receiving ongoing comprehensive care, given only limited care for some patients in our overall cohort. When comparing the DMFT scores from both groups to averages reported from the adult US population, both the total study cohort and the restorative patient subgroup had higher DMFT scores compared to the average US adult score (Table 3).

TABLE 3.

Comparison of decayed, missing, and filled tooth indices (DMFT) between average US adult cohort, the entire population included in this study (“Total Cohort”) and those patients receiving restorative procedures (“Restorative Patients”), which may represent those patients with ongoing treatment and more complete data.

	Average US adult score (n = 25,566)	Total cohort score (n = 248)	p vs. average	Restorative patients score (n = 152)	p vs. average	p Total cohort vs. restorative patients
Decayed	0.9 ± 0.05	1.6 ± 3.2	< 0.0001	2.0 ± 3.8	< 0.0001	0.21
Missing	1.9 ± 0.07	4.8 ± 6.8	< 0.0001	4.0 ± 5.2	< 0.0001	0.14
Filled	6.5 ± 0.11	6.7 ± 6.1	< 0.0001	9.0 ± 5.9	< 0.0001	0.0002

Note: Comparisons between groups made using paired t‐tests, statistically significant results highlighted.

During the 5‐year duration of our study, we identified six BAs taken by 10 or more individuals: adalimumab (Humira), infliximab (Remicade), etanercept (Enbrel), rituximab (Rituxan), dupilumab (Dupixent), and ustekinumab (Stelara). These most common agents accounted for 190 patients (76.9% of all patients), including 67 males, 122 females, and one of another gender identity, with an average year of birth of 1970. Five of these patients were simultaneously using two BAs. The BA with the most restorations varied over the years in the study. Etanercept (Enbrel) was the agent most correlated with restorative need in 2017, 2018, and 2020, while adalimumab (Humira) accounted for the largest number of restorations in 2017 (tied), 2019, and 2021, and patients on dupilumab (Dupixent) needed the most restorations in 2022. In 2020, there was a reduction in the number of restorations across all six agents, with a significant rise in 2021 and 2022 (Table 4). Of note, no patients taking rituximab received restorative treatments in 2022. Across the full cohort and in this subanalysis, some individuals received multiple restorative treatments within the study year, while others underwent only a single restorative treatment.

TABLE 4.

Number of restorations completed on subgroup of patients taking the most common biologic agents represented (those taken by > 10 patients) by year and across the entire study period.

	2017	2018	2019	2020	2021	2022	2017–2022
Dupilumab	1	1	7	11	23	21	64
Etanercept	8	27	19	17	17	6	94
Adalimumab	8	20	37	11	24	20	120
Infliximab	7	17	15	5	22	16	82
Rituximab	1	8	10	5	17	0	41
Ustekinumab	4	16	8	8	16	4	56

4. Discussion

Although there has been some previous research on the effects of BAs in the orofacial region, much of the existing evidence is theoretical, based on specialized settings, and comes from small sample sizes. Our study represents the first estimation of dental status in this population. In this way, this study begins to characterize the oral health of patients taking BAs through a focus on the periodontal and restorative treatment experiences of patients taking the three most common classes of biologics.

Within the BAs included (TNF‐α inhibitors, IL inhibitors, lymphocyte modulators), patients seen in our setting were treated with a range of medications (n = 24) for a wide variety of medical conditions (n = 32 distinct indications) representing each of the common classes of BAs included. While the spread of BAs has increased over time, there was not a clear trend of increasing patients across years included in this dataset. However, there was an increasing rate of periodontal and restorative treatments completed from 2017 to 2022, notably all without evidence of complications after treatment. It is possible that this could represent increased dental needs in this cohort, but may also represent increased presentation for care, findings that would benefit from additional studies to validate and further define these changes over time.

Our cohort exhibited a notable female predominance, as is expected in studies focused on autoimmune and inflammatory disorders, the primary indications for treatment in this population (Jacobson et al. 1997). This gender disparity has been attributed to various factors, including the influence of female hormones such as estrogen, prolactin, and progesterone interacting with receptors on immune regulatory cells (Cutolo et al. 2006; Oliver and Silman 2009). Additionally, females tend to seek medical attention more frequently when they notice changes in their health than their male counterparts, which can contribute to an exaggerated observed gender disparity (Thompson et al. 2016). Patients were included across age ranges, with the majority in their mid‐life.

Patients are generally recommended to undergo routine periodontal care consisting of either prophylaxis or targeted treatment as part of ongoing oral health maintenance, although the interval for this recommendation is variable depending on locality and is based on scant evidence (Fee et al. 2020). Over the course of the study, a maximum of 60% of patients receiving any form of care in our institution in a given year received some form of periodontal therapy, comprising both preventive and active care, with a total of 72.6% of the population receiving periodontal therapy at some point. The lack of any periodontal treatment in 27.4% of this population at high risk of infection may compromise oral health and the ability to diagnose and prevent developing periodontal and other orofacial problems (Patel et al. 2010). Of those who did receive periodontal care, our data suggest a similar rate of periodontal disease as in the general population (42.4% of this cohort, which includes any patient over 18 years of age vs. 42.2% of adults 30 and older in the United States) (National Institute of Dental and Craniofacial Research n.d.). Periodontal treatments received in patients taking BAs comprised all forms of care, with prophylaxis treatments being most common and periodontal surgeries and periodontal maintenance being completed rarely. This may further illustrate the distribution of periodontal need in this population, while the dearth of periodontal maintenance may relate to coding errors or lack of follow‐up after patients receive scaling and root planing.

Patients undergoing restorative treatment took a variety of BAs and presented for a range of restorative treatments, including all classes of treatment evaluated in this study. The overall rate of restorative treatment showed an upward trend over the study period, possibly suggesting increased treatment need over time for BAs. However, the proportion of active patients requiring restorative treatment did not rise above 36%. While there is no international standard for restorative needs in healthy adults, this represents a consistent yet high rate of dental treatment demands within our population. The entire study population had significantly higher scores for decayed, missing, and filled teeth compared to the average US adult score as reported by the CDC. This may reflect the known increased risk of infection in patients taking BAs, given the bacterial etiology of dental caries. A higher rate of filled teeth was found in those patients receiving any restorative treatment compared to our overall cohort. This could be because some patients were only seen for care for a short period of time or solely received limited care, while those receiving restorative treatments may have more complete data. While oral lesions are noted as a complication of taking BAs, no consistent connection to xerostomia during treatment with BAs exists in current literature (France et al. 2023). Rather, various BAs have been studied in Sjogren's syndrome for evidence of improved clinical salivary parameters as well as other clinical and laboratory measures (Gueiros et al. 2019). However, it is known that taking multiple medications simultaneously can lead to xerostomia (Soto and Meyer 2021). The majority of patients in this cohort were taking multiple medications, as is expected in populations with serious chronic disease. This could lead to a decrease in salivary flow, changes in salivary composition, and an increased rate of caries, although no direct evidence of salivary changes was available in the current dataset. Additionally, any underlying oral lesions or mucosal diseases as a result of the treated pathology, changes in range of motion, and other manifestations of medical conditions may interfere with patient ability to maintain meticulous oral hygiene, which could contribute to increases in both caries and periodontal disease. Although the current dataset is small and contains no internal control, these findings can be verified in future cohorts and may suggest a higher caries burden in this population.

Evaluating the most common agents within our data set revealed approximately 50% of the patients on common agents received restorative treatment each year, with high variability from 0% (rituximab, 2022) to 71% (ustekinumab, 2020). The variation in the number of patients undergoing restorations per BA per year does not necessarily imply an inherent variation in risk between the agents.

Our study provides the first characterization of the oral status of patients taking BAs in a single institution and, as such, suffers inherent limitations that set the stage for future research. As a retrospective study, there exists the potential for missing or inaccurate data. In our study, this limitation is evident in demographics and medical history, including missing data on the indication for BA therapy. It is also possible that other data is missing, including patients who may have incorrectly self‐reported their medications or if agents were entered inaccurately. This study is unable to account for dental treatment completed on these patients in other settings and, therefore, may not fully characterize the needs of these patients, particularly those who underwent limited care in our setting. Due to the heterogeneity of the population, we were unable to control our findings for other medical conditions or medications that may have influenced the patients' needs. We also only included patients above 18 years of age, which excludes any patients receiving BAs for childhood diseases, who may have unique needs during treatment. Additionally, it is noteworthy that our study used treatments received as a stand‐in for dental caries and periodontal disease. We must recognize that restorations, especially, can be attributed to various reasons other than caries, such as fractured teeth or developmental conditions that affect the teeth. Our data also reflect a limited scope of dental treatment. For future research, it would be beneficial to include additional dental needs, treatments, and diagnoses. Incorporating data from other institutions, larger cohorts, and with increased specification would enhance the validity of our findings, as would direct comparison of oral and dental status between patients taking BAs and matched patients not using these medications. Prospective cohorts of patients would also greatly enhance the quality of this data, including through the development of new dental needs and improved data capture on oral and systemic conditions. This additional data will benefit dental clinicians from all specialties as they see increasing numbers of patients taking BAs and presenting for routine dental treatments. Capturing and reporting dental needs and tolerance of treatment in these patients will allow for a better understanding of how to best and most safely treat this population, improving the service they can receive across dental medicine.

5. Conclusion

To the best of our knowledge, our study is the first to illustrate the dental needs of patients using BAs, providing an initial estimation of the treatment burden in this population. This study illustrates the periodontal and restorative treatment experiences of patients taking BAs at one institution, with a majority of patients across classes of BAs requiring both forms of treatment consistently and tolerating them without complication. While the limitations of the study population prevent generalization, this study adds to the literature on BAs by describing dental treatment needs over a 5‐year period. This study provides initial evidence that can inform our understanding of this population and requires additional clarification through future work in larger, multicenter cohorts.

Author Contributions

Shivani Shah: conceptualization, investigation, writing – original draft, writing – review and editing, visualization, formal analysis. Nila Veerabagu: conceptualization, investigation, writing – original draft, writing – review and editing, visualization, formal analysis. Nana A. A. Essel: investigation, writing – original draft, visualization. Neda Mahjour: conceptualization, investigation, writing – review and editing. Katherine France: conceptualization, investigation, writing – original draft, writing – review and editing, visualization, validation, methodology, software, formal analysis, project administration, data curation, resources, supervision.

Ethics Statement

This study was approved by the University of Pennsylvania Institutional Review Board as exempt with protocol #851121, which included waiver of individual patient consent as a retrospective chart review study.

Conflicts of Interest

The authors declare no conflicts of interest.

Appendix A. List of Biologic Agents Queried to Identify Patients for Inclusion in This Study, Comprising Generic and Brand Names of Tumor Necrosis Factor (TNF)‐Alpha Antagonists, Interleukin Inhibitors, and Lymphocyte Modulators

TNF‐Alpha Inhibitors

Generic names: Adalimumab, adalimumab‐adbm, adalimumab‐atto, adalimumab‐bwwd, adalimumab‐adaz, etanercept, etanercept‐szzs, infliximab, infliximab‐abda, infliximab‐dyyb, infliximab‐qbtx, golimumab, certolizumab, certolizumab pegol, CTP‐13.

Brand names: Humira, Enbrel, Remicade, Simponi, Cimzia, Simponi Aria, Inflectra, Amjevita, Renflexis, Hulio, Avsola, Yusimry, Ixifi, Hyrimoz, Hadlima, Eticovo, Erelzi, Cyltezo, Abrilada, Remsima.

Interleukin Inhibitors

Generic names: Anakinra, basiliximab, benralizumab, bimekizumab, brodalumab, briakinumab, canakinumab, dupilumab, daclizumab, guselkumab, ixekizumab, mepolizumab, reslizumab, risankizumab, risankizumab‐rzaa, rilonacept, satralizumab, sarilumab, secukinumab, siltuximab, sirukumab, tildrakizumab, tildrakizumab‐asmn, tralokinumab, tocilizumab, ustekinumab.

Brand names: Actemra, Arcalyst, Adbry, Cinqair, Cosentyx, Dupixent, Enspryng, Fasenra, Ilumya, Ilaris, Kevzara, Kineret, Nucala, Siliq, Sirukumab, Skyrizi, Stelara, Sylvant, Simulect, Taltz, Tremfya, Zenapax, Zinbryta.

Lymphocyte Modulators

Generic names: Venclexta, rituximab, ocrelizumab, ofatumumab, epratuzumab, belimumab, briobacept, blisibimod, atacicept, tebentafusp‐tebn, ublituximab, obintuzumab, inebilizumab, obexelimab, ianalumab, telitacicept, tolebrutinib, evobrutinib, ibrutinib, idelalisib, acalabrutinib, zanubrutinib, duvelisib, abatacept, ipilimumab.

Brand names: Venetoclax, Rituxan, Benlysta, Kimmtrak, Imbruvica, Calquence, Brukinsa, Kesimpta, Ocrevus, Lymphocide, Uplizna, Gazyva, Copiktra, Zydelig, Imbruvica, Orencia, Yervoy.

Data Availability Statement

Data presented in this paper is available upon reasonable request to the corresponding author.