Recent research analyzed factors influencing the selection of the first-line biologic medications and the real-life factors that lead to switching from those medications to other biologics in treating rheumatoid arthritis (RA). The study compared the use of abatacept and tocilizumab with a tumor necrosis factor alpha inhibitor (TNFi).1,2 Participants were enrolled in the Lombardy Rheumatology Network (LORHEN) after Jan. 1, 2010, and were treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) at eight rheumatology centers in Northern Italy.
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The study population (n=1,910) was divided into first- and second-line bDMARD treatment groups, with 1,264 first-line patients (115 received abatacept, 130 received tocilizumab and 1,019 received a TNFi) and 646 second-line patients (143 received abatacept, 97 received tocilizumab and 406 received a TNFi).
A majority of participants initiating bDMARDs received a TNFi. Comorbidities that influenced the choice toward abatacept and tocilizumab compared with a TNFi were categorized by organ system groups: arterial hypertension, cardiovascular disease, diabetes mellitus, dyslipidemia, osteoporosis, peripheral neuropathy, pulmonary disease, thyroid autoimmune disease and other comorbidities not belonging to the prior categories.
In general, older patients were more likely to be prescribed abatacept and tocilizumab compared with patients receiving a TNFi (P<0.0001). A higher prevalence of positive latent tuberculosis infection (LTBI) was associated with abatacept (30%) than with tocilizumab (16%) or TNFi (16%). Combination treatment with methotrexate was lower in tocilizumab-treated patients.
Analysis showed a prevalence of prescribing abatacept in patients who were receiving it as a second-line treatment; were older; had dyslipidemia, pulmonary disease or other comorbidities; and had extra-articular manifestations of RA. Use of tocilizumab was linked to second-line treatment, older age and more severe disease activity. If the first bDMARD was stopped due to an adverse event, this factor influenced a subsequent treatment choice toward abatacept.
In this study, older age and comorbidities influenced changing treatment to abatacept and tocilizumab vs. a TNFi. After patients initially failed first-line treatment with a TNFi, switching to an agent with a different mechanism of action was more widespread.
Insights into Drug-Related Interactions in Older Adults
In a recent cross-sectional study, researchers evaluated the prevalence of possible drug–disease and drug–drug interactions and associated variables in community-dwelling older adults.3 Patients aged 70–79 years (n=3,055) without mobility limitation at their baseline visit in the Health Aging and Body Composition Study were enrolled in this study.
Outcome factors were potential drug–disease and drug–drug interactions identified by using particular criteria from various sources, as well as self-reported nonprescription and prescription drug use. Explicit criteria for 70 potential drug–drug interactions developed by geriatric experts and reactions found to be a cause for drug-related hospitalizations were used.
The findings showed that 34% of patients (34.1%) had at least one interaction, while 25.1% had at least one drug–drug interaction. Also, 10.7% of patients who had a drug–drug interaction involved a nonprescription drug. Sixteen percent of patients had a potential drug–disease interaction, with at least 37% of those reactions involving a nonprescription drug.
Non-steroidal anti-inflammatory drugs (NSAIDs) and anti-hypertensive agents were the most common drug–drug interaction. Aspirin/NSAID use in patients with a history of peptic ulcer disease without the use of gastro-protection (4.3%) was the most common drug–disease interaction. Having a history of falls or fractures and taking one of five central nervous system medication classes (4%; e.g., anticonvulsants, antipsychotics, SSRIs, TCAs, benzodiazepine receptor agonists) was the second most common drug–disease interaction.
Two factors were associated with drug interactions: a history of hospitalization in the prior year and the number of medications used. The use of each prescription drug raised the likelihood of having at least one type of drug interaction by 35–40%. In patients with a prior hospitalization, hospitalization raised the odds of having at least one type of drug interaction by 49–84%.
The authors write that the ability to generalize this study to the older U.S. population may be limited because the study participants did not have mobility issues, heart failure or chronic kidney disease. Thus, the rate of drug interactions observed in this study may be low. More research is needed in this area, especially in patients with more comorbidities.
Older patients were more likely to be prescribed abatacept & tocilizumab compared with patients receiving a TNFi.
Piclidenoson Studied in Autoimmune Diseases
Piclidenoson is an oral, A3 adenosine receptor antagonist (A3AR) currently in clinical trials for autoimmune diseases, including psoriasis (Phase 2/3) and rheumatoid arthritis (RA).4 This agent was developed and is being investigated as a first-line therapy and replacement for methotrexate, the current standard of care for RA.
Phase 2 clinical trials for RA are completed. Piclidenoson is scheduled to enter Phase 3 trials this year for both RA and psoriasis. ACRobat, a Phase 3 randomized, double-blind, active and placebo-controlled clinical trial of piclidenoson, has begun patient enrollment for 500 patients in Europe, Canada and the U.S.
The Phase 3 study’s primary endpoint is a decrease in disease activity score (DAS) after Week 12 of treatment with 1 mg or 2 mg piclidenoson given twice daily compared with weekly doses of methotrexate and placebo. Secondary endpoints will include ACR20, ACR50 and ACR70 scores.5 The total study duration will be 24 weeks to provide additional data on long-term efficacy and safety.
Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- Monti S, Klersy C, Gorla R, et al. Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: Real-life data from the Italian LORHEN Registry. Clin Rheumatol. 2017 Jan 5. doi:10.1007/s10067-016-3528-y. [Epub ahead of print]
- Cohen S. Perspective: Comorbidities, older age may influence choice of abatacept. Healio. 2017 Jan 20.
- Hanlon JT, Perera S, Newman AB, et al. Potential drug–drug and drug–disease interactions in well-functioning community-dwelling older adults. J Clin Pharm Ther. 2017 Jan 22. doi: 10.1111/jcpt.12502. [Epub ahead of print]
- Can-Fite BioPharma Ltd. Can-Fite gears up for ACRobat, its Phase III trial of piclidenoson in rheumatoid arthritis. 2017 Feb 8.
- BioNap Inc. Can-Fite phase 3 RA program ready to start. 2017 Feb 8.