Dental Implants for Patients Using TNF-Alpha Inhibitors

Overseen by Katherine France, DMD, MBE

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

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

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The goal of this pilot study is to learn about healing after dental implant placement in patients taking a class of biologic drug called Tumor Necrosis Factor or TNF-alpha antagonist or inhibitor. The main questions it aims to answer are: Do patients taking TNF-alpha inhibitors have any complications after the placement of dental implants? Do patients taking TNF-alpha inhibitor experience increased pain after dental implant placement compared to the expected levels when healing from this procedure? Researchers will recruit patients both taking these drugs and those not taking these drugs to compare the outcomes between the two groups. Participants missing teeth will be recruited to receive dental implants to meet ideal dental status and will be followed before and after the implant placement to determine levels of health and ensure proper healing. Participants will be followed for a total of one year and follow up visits will consist of both clinical examination and radiographs (x-rays) to evaluate bone level and implant status. Participants will also be asked to rate their pain during clinic visits and at home on a diary and record the amount of pain control medication they take after the implant procedure.

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 data supports the effectiveness of TNF-alpha inhibitors for dental implants in patients using these drugs?

TNF-alpha inhibitors, like certolizumab pegol, infliximab, and adalimumab, have been shown to be effective in treating conditions like rheumatoid arthritis and other inflammatory diseases by reducing joint damage and improving quality of life. This suggests they may help manage inflammation, which could be beneficial for dental implant success in patients using these drugs. ^{1 2 3 4 5}

Are TNF-alpha inhibitors generally safe for humans?

TNF-alpha inhibitors, such as infliximab, adalimumab, and etanercept, are generally considered safe and well-tolerated, though they can cause some adverse skin reactions. They have been used successfully for various inflammatory and autoimmune conditions, and their safety profile is favorable when proper safety measures are taken before and during treatment. ^{2 3 6 7 8}

How do TNF-alpha inhibitor drugs differ from other treatments for dental implants?

TNF-alpha inhibitors are unique because they are biological agents that specifically target and block a protein involved in inflammation, which is different from traditional treatments that may not target this specific pathway. These drugs are typically used for chronic inflammatory conditions like rheumatoid arthritis and Crohn's disease, and their use in dental implants is novel, as there are no standard treatments specifically for patients using TNF-alpha inhibitors in this context. ^{2 5 6 9 10}

Research Team

Katherine France, DMD, MBE

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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 can read and speak English.

I am over 18 years old.

Exclusion Criteria

I have severe gum disease with deep pockets or significant bone loss.

My dental scans show a cyst or tumor in my jaw.

I am currently taking medication to prevent bone loss or to stop the formation of new blood vessels.

Trial Timeline

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

Treatment Details

Interventions

• TNF-Alpha Inhibitors (Cytokine Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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]

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-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]

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]

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]

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]

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, 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety? [2016]

4. England pubmed.ncbi.nlm.nih.gov

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. [2020]

5. Australia pubmed.ncbi.nlm.nih.gov

Clinical use of anti-TNF-alpha biological agents--a guide for GPs. [2015]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Update upon efficacy and safety of TNF-α inhibitors. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the tumor necrosis factor antagonists. [2016]

9. Canada pubmed.ncbi.nlm.nih.gov

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

10. New Zealand pubmed.ncbi.nlm.nih.gov

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