Dental Implants for Patients Using TNF-Alpha Inhibitors

Overseen By Katherine France, DMD, MBE

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must be taking: TNF-alpha inhibitors

Must not be taking: Antiresorptives, Antiangiogenics

Disqualifiers: Periodontal disease, Uncontrolled diabetes, Tobacco use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well dental implants heal in people taking TNF-alpha inhibitors, medications often used for conditions like rheumatoid arthritis. The researchers aim to determine if these patients experience more complications or pain during healing compared to those not on these medications. Participants needing dental implants and who have taken TNF-alpha inhibitors for at least six months may be eligible, provided they do not have complicating health issues like uncontrolled diabetes or recent tobacco use.

As an unphased trial, this study offers a unique opportunity to contribute to understanding dental implant healing in patients using TNF-alpha inhibitors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking TNF-alpha inhibitors, you must have been on a stable dose for at least 6 months to participate.

What prior data suggests that dental implants are safe for patients using TNF-alpha inhibitors?

Research has shown that TNF-alpha inhibitors, such as infliximab, adalimumab, and etanercept, are generally safe and well-tolerated. These medications often treat conditions like rheumatoid arthritis by blocking a substance in the body that causes inflammation. Although mostly safe, they can sometimes cause skin problems or reactivate a hidden lung infection called latent tuberculosis.

Most people using these medications do not experience serious issues, but awareness of possible side effects is important. Prospective trial participants should consider these facts to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how dental implants perform in patients using TNF-alpha inhibitors, a class of drugs commonly used to treat autoimmune conditions like rheumatoid arthritis. Typically, dental implant success can be influenced by various factors, and there is limited information on how TNF-alpha inhibitors might affect this success. This trial aims to discover whether patients on these medications face any unique challenges or benefits when receiving dental implants, potentially leading to tailored care strategies. By comparing patients on TNF-alpha inhibitors to those who aren't, researchers hope to understand any differences in healing or implant success, which could improve outcomes for individuals using these medications.

What evidence suggests that dental implants are effective for patients using TNF-alpha inhibitors?

Studies have shown that TNF-alpha inhibitors effectively treat conditions like rheumatoid arthritis and Crohn's disease. These drugs block a protein called tumor necrosis factor (TNF), reducing inflammation in the body. Some research suggests TNF-alpha inhibitors might affect dental health, linking them to a higher risk of healing problems, such as in gum disease cases. However, their effect on healing after dental implants remains unclear. This trial will compare patients taking TNF-alpha inhibitors with those not taking these drugs to investigate their influence on the healing process after dental implants, focusing on complications and pain levels. ^{1 2 6 7 8}

Who Is on the Research Team?

Katherine France, DMD, MBE

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for individuals missing teeth who are either taking TNF-alpha inhibitors, a type of biologic drug, or not on these medications. They should be seeking dental implants and willing to participate in follow-ups including x-rays and pain assessments over a year.

Inclusion Criteria

I am healthy enough for surgery to place an implant.

I have been on a stable dose of TNF-alpha inhibitor for at least 6 months.

Patients must provide independent consent for medical procedures or attend study visits with a surrogate decision maker

Exclusion Criteria

Uncontrolled diabetes (HbA1c >8.0)

Routine tobacco or tobacco product use in the last 1 year

Patients with periodontal disease (periodontal pockets above 4mm or evidence of horizontal bone loss more than mild severity)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implant Placement

Dental implants are placed under standard surgical approach and followed by immediate post-operative care

1 day

1 visit (in-person)

Follow-up

Participants are monitored for healing, pain, and systemic inflammation through clinical exams and radiographs

12 months

Visits at 1 week, 1 month, 3 months, 6 months, and 12 months (in-person)

Pain and Inflammation Monitoring

Participants' pain levels and systemic inflammation markers are assessed through patient diaries and blood tests

12 months

Blood tests at implant visit and follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• TNF-Alpha Inhibitors

Trial Overview The study aims to compare the healing process and pain levels after dental implant placement between patients using TNF-alpha inhibitors and those who aren't. It involves clinical exams, x-rays, pain diaries, and tracking medication use post-procedure.

How Is the Trial Designed?

Group I: Patients taking TNF-alpha inhibitors Experimental Treatment 1 Intervention

Adult patients (18 years of age or older) taking a TNF-alpha inhibitor as defined by the NIH and missing teeth will be recruited to receive dental implant placement according to standard of care for ideal dental restoration. Patients must have been taking a stable dose of the drug for at least 6 months and have no contra-indications to implant placement (regular tobacco use in the last year, periodontal disease, pathology in the jaw bone(s), history of head and neck radiation, history of antiresorptive or antiangiogenic agents, uncontrolled diabetes, pregnancy, other medical conditions that preclude safe delivery of outpatient medical care) to be eligible for enrollment in the study.

Group II: Patients not taking TNF-alpha inhibitors Experimental Treatment 1 Intervention

Patients over age 18 not taking TNF alpha inhibitors will be recruited and matched via age and sex to the patients taking TNF-alpha inhibitors. The general exclusion criteria (regular tobacco use in the last year, periodontal disease, pathology in the jaw bone(s), history of head and neck radiation, history of antiresorptive or antiangiogenic agents, uncontrolled diabetes, pregnancy, other medical conditions that preclude safe delivery of outpatient medical care) will apply to both arms equally.

TNF-Alpha Inhibitors is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as TNF-alpha inhibitors for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis

Approved in United States as TNF-alpha inhibitors for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Canada as TNF-alpha inhibitors for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis

Approved in Japan as TNF-alpha inhibitors for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Nobel Biocare

Industry Sponsor

Trials

28

Recruited

2,800+

Published Research Related to This Trial

TNF-alpha inhibitors, including infliximab, adalimumab, and etanercept, have been shown to be effective in treating inflammatory and immune-mediated diseases, either alone or in combination with other treatments.

While the safety and efficacy profiles of these TNF-alpha inhibitors are generally similar, there may be specific differences among the three agents that could influence treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-TNF-alpha inhibitors: a new therapeutic approach for inflammatory immune-mediated diseases: an update upon efficacy and adverse events. Murdaca, G., Colombo, BM., Puppo, F.[2022]

TNF-α inhibitors like infliximab and adalimumab are effective treatments for various chronic inflammatory diseases, but the development of neutralizing antibodies against these drugs can reduce their efficacy and increase the risk of adverse events.

Co-administering DMARDs such as methotrexate or leflunomide can help prevent the formation of these neutralizing antibodies, thereby improving the overall effectiveness and safety of TNF-α inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety? Murdaca, G., Spanò, F., Contatore, M., et al.[2016]

Anti-TNF-alpha therapies, while generally safe and effective for treating autoimmune disorders, can lead to adverse skin reactions, as observed in 5 patients who developed erythematous annular plaques while on different TNF-alpha inhibitors.

Skin biopsies from these patients revealed interstitial granulomatous dermatitis, which resolved completely after discontinuation of the medications, highlighting the need for awareness of this potential side effect in patients receiving anti-TNF-alpha therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors. Deng, A., Harvey, V., Sina, B., et al.[2018]

TNF-alpha inhibitors, including infliximab, adalimumab, etanercept, and golimumab, are effective new treatment options for psoriasis and psoriatic arthritis, significantly improving patient quality of life.

These therapies have a favorable safety profile when proper screening and monitoring are conducted, making them a valuable addition to psoriasis treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the tumor necrosis factor antagonists. Bachmann, F., Nast, A., Sterry, W., et al.[2016]

Certolizumab pegol is effective in treating rheumatoid arthritis (RA), showing significant improvements in patient outcomes such as joint function and disease activity, based on a systematic review of 11 trials involving 4,324 patients.

While certolizumab pegol demonstrated benefits, it was associated with a higher rate of serious adverse events compared to placebo, indicating a need for careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Ruiz Garcia, V., Jobanputra, P., Burls, A., et al.[2020]

Certolizumab pegol (CZP) is effective in treating rheumatoid arthritis (RA), showing significant improvements in symptoms and quality of life, with a 25% absolute improvement in ACR50 response and a 10% increase in remission rates based on a review of 14 trials involving over 5400 participants.

While CZP is associated with a higher rate of serious adverse events compared to placebo, the overall risk is clinically significant but not statistically significant, indicating that while it is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Ruiz Garcia, V., Burls, A., Cabello, JB., et al.[2020]

Tumor necrosis factor (TNF)-α inhibitors, including infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol, are now clinically available and represent a significant advancement in treating immune-mediated and inflammatory diseases.

The editorial highlights the importance of understanding pretreatment considerations and potential adverse events associated with TNF-α inhibitors, as well as specific recommendations for their use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update upon efficacy and safety of TNF-α inhibitors. Murdaca, G., Colombo, BM., Cagnati, P., et al.[2022]

TNF-alpha inhibitors are effective biological agents for treating chronic inflammatory conditions like rheumatoid arthritis, showing strong potential to reduce inflammation and induce remission when traditional treatments fail.

While these drugs can be very effective, they come with an increased risk of infections and other serious side effects, necessitating careful monitoring and specialist oversight in their prescription.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of anti-TNF-alpha biological agents--a guide for GPs. Chang, J., Girgis, L.[2015]

Blockade of tumor necrosis factor (TNF) with agents like etanercept, infliximab, and adalimumab has shown comparable effectiveness in treating rheumatoid arthritis (RA), based on data from noncomparative trials.

Etanercept and infliximab not only help with RA but also show beneficial effects in other inflammatory conditions such as psoriatic arthritis and ankylosing spondylitis, with infliximab being particularly effective for certain granulomatous diseases like Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiating the efficacy of tumor necrosis factor inhibitors. Haraoui, B.[2015]

The introduction of TNF-alpha inhibitors like infliximab and etanercept for treating rheumatoid arthritis (RA) in Denmark could significantly improve patients' quality of life by reducing disease activity and preventing joint damage.

However, implementing these treatments could lead to substantial additional costs for the Danish healthcare system, estimated between €67-188 million for a progressive treatment approach and €17-49 million for a more modest approach over five years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The case of tumour necrosis factor-alpha inhibitors in the treatment of rheumatoid arthritis: a budget impact analysis. Sørensen, J., Andersen, LS.[2018]

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