Abatacept, tofacitinib show potential in treatment of sarcoidosis
Use of off-label therapies could benefit patients with hard-to-treat disease
Among people with sarcoidosis who failed to respond to earlier lines of treatment, the use of abatacept or tofacitinib — medications approved for other inflammatory conditions — appeared safe and effective, according to a Danish report.
While neither abatacept (sold as Orencia in the U.S. and Europe) nor tofacitinib (sold as Xeljanz) has been granted regulatory approval for sarcoidosis, these therapies are sometimes used off-label, meaning for a condition for which they’re not approved, as a treatment for the immune system disease.
In this study, the medications were used in more than 50 people with sarcoidosis.
“To our knowledge, this is the largest observational study documenting the drug survival, safety, and treatment responses of abatacept and tofacitinib in sarcoidosis patients,” the researchers wrote.
The study, “Abatacept and tofacitinib in refractory sarcoidosis: drug survival, safety, and treatment response,” was published in Clinical and Experimental Rheumatology.
Off-label therapies show possible benefits in hard-to-treat sarcoidosis
Sarcoidosis is characterized by the accumulation of granulomas, or small clumps of immune cells, in the body’s tissues. First-line treatment usually involves corticosteroids, a class of potent anti-inflammatory medications.
In Denmark, where the study was conducted, second-line treatment when corticosteroids are insufficient includes disease-modifying anti-rheumatic drugs, such as the chemotherapy agent methotrexate. Where this fails, biological therapies, often TNF inhibitors (TNFi), are used. Among such medications are infliximab (sold as Remicade) and adalimumab (sold as Humira).
Still, some patients will not respond, or be refractory, even to TNF inhibitors, prompting clinicians to try other off-label options — even ones that don’t have as much clinical data to back them.
One such treatment is abatacept, which works to inhibit the activation of a class of immune cells called T-cells. A small clinical trial to test the injectable therapy in people with treatment-resistant sarcoidosis was completed in Germany (EudraCT: 2016-003360-39), but the results haven’t been published.
Another option is tofacitinib, an oral medication that works by inhibiting an enzyme called Janus kinase that’s involved in immune cell function. Some small case studies have reported its possible benefits in sarcoidosis.
More than two-thirds of patients responded to the treatments
In this study, scientists from Copenhagen University Hospital Rigshospitalet described clinical outcomes from 41 adult sarcoidosis patients who were treated with abatacept as a third-line therapy, as well as 12 patients given tofacitinib as a fourth-line therapy.
In both groups, the most commonly affected tissues were in the lungs or lymph nodes (33%-44%), followed by joints or muscles (17%-20%), and the brain or spinal cord (17%-33%).
Most patients in both the abatacept and tofacitinib groups had been previously treated with methotrexate (75%-76%), and nearly all (92%-95%) had been given TNFi.
When starting abatacept or tofacitinib, nearly a quarter in either group were simultaneously receiving methotrexate and about 60% were taking prednisolone, a corticosteroid. Of the 12 people on tofacitinib, 10 had been previously treated with abatacept.
For those on abatacept, 92% were still on the therapy after six months, and 82% were on it after a year. Over a median of about 1.75 years of follow-up, 14 people discontinued treatment. Four stopped due to adverse events and eight due to no treatment effect.
Nearly three-quarters of patients — 71%, or 29 of 39 evaluated patients — were considered treatment responders, which was determined by a clinician based on a number of clinical outcomes.
For those on tofacitinib, 89% of patients were still on treatment after six months, and 74% remained on it after a year. Two people stopped treatment over a median follow-up of 7.5 months, both due to a lack of treatment effect.
Two-thirds of tofacitinib-treated patients — 67%, or six of nine people evaluated — were considered treatment responders.
We find that patients treated with both abatacept and tofacitinib … achieved high response rates and that both drugs represent good and safe therapeutic options in sarcoidosis [patients] refractory to previous TNFi therapy.
For both treatment groups, involvement of organs outside the brain and spinal cord (e.g., eyes, joints/muscles, or bone) was more prevalent among treatment responders, while nonresponders had a higher prevalence of brain or spinal cord involvement. Concomitant use of prednisolone and methotrexate was also linked to higher response rates.
In general, there were no significant deteriorations in lung function observed for treated patients in either group.
With both abatacept and tofacitinib, some patients were able to completely taper off corticosteroids after starting treatment, with significant reductions in the prednisolone dose observed after six months.
Significant reductions in blood levels of sIL-2R, a sarcoidosis disease biomarker, also were observed after the start of treatment in both groups.
“In conclusion, we find that patients treated with both abatacept and tofacitinib … achieved high response rates and that both drugs represent good and safe therapeutic options in sarcoidosis [patients] refractory to previous TNFi therapy,” the researchers wrote.
The team noted that their use of abatacept as an earlier line of treatment than tofacitinib is mainly a result of the timeline on which the treatments were developed.
“It is likely that the effect of these drugs is equal and that other factors in the future should decide the order of treatment, such as economy, types of organs involved, and patient preferences,” the researchers wrote, though noting that the design of the study was not suitable to directly compare the treatments.
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