JAK Inhibitors Edge Out Anti-TNFs for Pain Relief in Rheumatoid Arthritis

Targeted drugs for rheumatoid arthritis (RA) are not created equal when it comes to pain relief, a retrospective study from Sweden indicated, although the differences appeared to be modest.

Three months after starting a new targeted RA therapy, patients on Janus kinase (JAK) inhibitors reported decreases in pain that were an average of 4.0 points greater (95% CI 1.6-6.3) on a 100-point scale compared with those using tumor necrosis factor (TNF) inhibitors, according to Anna Eberhard, MD, of Lund University in Malmö, Sweden, and colleagues. The difference reflected adjustments for patient demographics, disease characteristics, and previous and current treatments.

“Similar trends” that fell short of statistical significance were also seen when JAK inhibitors were compared with less popular types of biologic therapy, such as interleukin (IL)-6 inhibitors, the T-cell inhibitor abatacept (Orencia), and the B-cell depletion agent rituximab (Rituxan), the researchers reported in Arthritis & Rheumatology.

The advantage for JAK inhibitors was especially pronounced, Eberhard and colleagues observed, when these agents were used alone and in patients who had previously tried other types of treatment. But for patients starting their first-ever targeted therapy, IL-6 inhibitors such as tocilizumab (Actemra) came out on top, with 3-month pain scores falling 10 to 12 points more than scores seen with JAK inhibitors, anti-TNFs, or rituximab.

Eberhard’s group also looked at pain scores 12 months after starting therapy, although these data weren’t collected for well over half of patients initially included. For those staying on treatment for that long, achievement of “low pain” (scores less than 20 out of 100) was numerically greater with JAK inhibitors than with anti-TNF inhibitors or anti-IL-6 drugs. But the differences, in the range of 3.3 to 3.5 points, didn’t quite reach statistical significance. Patients on abatacept and rituximab had about the same rate of low pain as did those on JAK inhibitors.

Pain is the most significant patient-centered aspect of RA, and while clinical assessment tools such as the Clinical Disease Activity Index (CDAI) include pain measures, they are not particularly emphasized. Drug efficacy studies generally use these composite measures as primary endpoints, while pain by itself is typically a secondary outcome if it’s reported at all. Eberhard and colleagues noted that “only limited results are available from observational studies comparing the effectiveness” of biologic RA drugs and JAK inhibitors for pain relief.

The current study drew on the Swedish Rheumatology Quality Register, which captures about 95% of all Swedes with RA treated with advanced therapies. Eberhard and colleagues analyzed those registry members starting one of the five drug classes during 2017-2019, a total of 8,430 individuals. In addition to pain ratings, the data included dates of starting and stopping therapy, concomitant treatments such as methotrexate and steroids, and measures of disease severity and clinical responses. Other national registries supplied data on comorbidities, hospitalizations, and other parameters that were used in the researchers’ statistical adjustments.

More than 75% of the cohort started a TNF inhibitor during the selected time frame. For the rest, JAK inhibitors were the most common (1,827 patients; 82% baricitinib [Olumiant]), followed by rituximab (n=1,149), abatacept (n=1,102), and anti-IL-6 drugs (n=887, 80% tocilizumab). Mean patient age was about 60, and approximately 80% were women.

Mean pain ratings at baseline stood at 56 to 65 among the five treatment types. After 3 months of treatment, the average reduction was in the range of 17 to 20 points, although the crude differences between drug types bore almost no resemblance to those seen after the statistical adjustments — a necessary step to account for the factors influencing treatment choices.

Most patients were able to stay with treatment once starting it, with retention rates of about 60% to 80% through 12 months (rituximab had the highest retention and IL-6 inhibitors the lowest). Also, pain relief seemed to correlate with overall efficacy. Standard assessments showed close to half of patients with “low pain” at 12 months in clinical remission and another one-third had low disease activity — an overall response rate of 80% to 85% for all five drug types.

The most important limitation to the study was that collection of important data was often spotty. Baseline pain scores were missing for roughly one-third of patients, and more than half had insufficient pain data at months 3 and 12. Also, not every potentially relevant factor was captured in the registries, leaving room for unmeasured confounding. Furthermore, treatment patterns in Sweden likely differ from other countries including the U.S., possibly limiting the study’s generalizability.